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Title: CCR5 promoter activity correlates with HIV disease progression by regulating CCR5 cell surface expression and CD4 T cell apoptosis.
Creator: Joshi, Anjali, Punke, Erin B., Sedano, Melina, Beauchamp, Bethany, Patel, Rima, Hossenlopp, Cassady, Alozie, Ogechika K., Gupta, Jayanta, Mukherjee, Debabrata, Garg, Himanshu
Abstract / Description: CCR5 is the major co-receptor for HIV and polymorphisms in the CCR5 gene as well as promoter region that alter cell surface expression have been associated with disease progression. We determined the relationship between CCR5 promoter polymorphisms and CD4 decline and other immunopathological features like immune activation and CD4+ T cell apoptosis in HIV patients. CCR5 promoter haplotype HHC was significantly associated with higher CD4 counts in patients. The relative promoter activity (RPA...
Show moreCCR5 is the major co-receptor for HIV and polymorphisms in the CCR5 gene as well as promoter region that alter cell surface expression have been associated with disease progression. We determined the relationship between CCR5 promoter polymorphisms and CD4 decline and other immunopathological features like immune activation and CD4+ T cell apoptosis in HIV patients. CCR5 promoter haplotype HHC was significantly associated with higher CD4 counts in patients. The relative promoter activity (RPA) of each haplotype was determined in vitro and combined promoter activity based on both alleles (CRPA) was assigned to each patients. Interestingly, CCR5 CRPA correlated inversely with CD4 counts and CD4:CD8 ratio specifically in viremic patients. In normal individuals, the CRPA correlated with the number of CCR5+ CD4+ T cells in the peripheral blood suggesting an effect on CCR5 expression. In a subset of high viremic patients harboring R5 tropic HIV, there was a strong correlation between CCR5 CRPA and both CD4 counts and CD4 T cell apoptosis. Our study demonstrates that, CCR5 promoter polymorphisms correlate with CD4 T cell loss possibly by regulating CD4 T cell apoptosis in HIV patients. Furthermore, assigning CRPAs to each patient is a new method of translating genotype to phenotype.
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Date Issued: 2017-12-22
Identifier: 10.1038/s41598-017-00192-x, fgcu_ir_000078, http://www.nature.com/articles/s41598-017-00192-x
Format: Citation

Title: Differences in Candidate Gene Association between European Ancestry and African American Asthmatic Children.
Creator: Gupta, Jayanta, Baye, Tesfaye M., Kovacic, Melinda Butsch, Biagini Myers, Jocelyn M., Martin, Lisa J., Lindsey, Mark, Patterson, Tia L., Hua, He, Ericksen, Mark B., Tsoras, Anna...
Show moreGupta, Jayanta, Baye, Tesfaye M., Kovacic, Melinda Butsch, Biagini Myers, Jocelyn M., Martin, Lisa J., Lindsey, Mark, Patterson, Tia L., Hua, He, Ericksen, Mark B., Tsoras, Anna M., Lindsley, Andrew, Rothenberg, Marc E., Wills-Karp, Marsha, Eissa, N. Tony, Borish, Larry, Khurana Hershey, Gurjit K.
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Abstract / Description: Candidate gene case-control studies have identified several single nucleotide polymorphisms (SNPs) that are associated with asthma susceptibility. Most of these studies have been restricted to evaluations of specific SNPs within a single gene and within populations from European ancestry. Recently, there is increasing interest in understanding racial differences in genetic risk associated with childhood asthma. Our aim was to compare association patterns of asthma candidate genes between...
Show moreCandidate gene case-control studies have identified several single nucleotide polymorphisms (SNPs) that are associated with asthma susceptibility. Most of these studies have been restricted to evaluations of specific SNPs within a single gene and within populations from European ancestry. Recently, there is increasing interest in understanding racial differences in genetic risk associated with childhood asthma. Our aim was to compare association patterns of asthma candidate genes between children of European and African ancestry.
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Date Issued: 2011-02-28
Identifier: fgcu_ir_000725
Format: Document (PDF)

Title: Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study.
Creator: Gupta, Jayanta, Dominic, Elizabeth A., Fink, Jeffrey C., Barrows, Ian R., Townsend, Raymond R., Joffe, Marshall M., Rosas, Sylvia E., Wolman, Melanie, Patel, Samir S., Keane,...
Show moreGupta, Jayanta, Dominic, Elizabeth A., Fink, Jeffrey C., Barrows, Ian R., Townsend, Raymond R., Joffe, Marshall M., Rosas, Sylvia E., Wolman, Melanie, Patel, Samir S., Keane, Martin G., Feldman, Harold I., Kusek, John W., Raj, Dominic S.
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Abstract / Description: Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.
Date Issued: 2015-04-24
Identifier: fgcu_ir_000702
Format: Document (PDF)

Title: Assessment of oral health knowledge, practices, and attitudes towards oral health and professional dental care among rural population in the Dominican Republic: a cross-sectional study.
Creator: Kahar, Payal, Tisone, Christine A.
Abstract / Description: Assessing oral health knowledge, attitudes and behaviors provide baseline information for developing health education programs. However, knowledge does not always translate into attitudes and practices and there is disconnect between them. Purpose: This study looked at oral health knowledge, attitudes, behaviors and dental care attendance among adult rural Dominicans, measured the caries prevalence and found the association of knowledge with the study variables.
Date Issued: 2015-01-01
Identifier: fgcu_ir_000728
Format: Document (PDF)

Title: Functional Variant in the Autophagy-Related 5 Gene Promotor is Associated with Childhood Asthma.
Creator: Gupta, Jayanta, Martin, Lisa J., Jyothula, Soma S. S. K., Butsch Kovacic, Melinda, Biagini Myers, Jocelyn M., Patterson, Tia L., Ericksen, Mark B., He, Hua, Gibson, Aaron M.,...
Show moreGupta, Jayanta, Martin, Lisa J., Jyothula, Soma S. S. K., Butsch Kovacic, Melinda, Biagini Myers, Jocelyn M., Patterson, Tia L., Ericksen, Mark B., He, Hua, Gibson, Aaron M., Baye, Tesfaye M., Amirisetty, Sushil, Tsoras, Anna M., Sha, Youbao, Eissa, N. Tony, Khurana Hershey, Gurjit K.
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Abstract / Description: Autophagy is a cellular process directed at eliminating or recycling cellular proteins. Recently, the autophagy pathway has been implicated in immune dysfunction, the pathogenesis of inflammatory disorders, and response to viral infection. Associations between two genes in the autophagy pathway, ATG5 and ATG7, with childhood asthma were investigated.
Date Issued: 2012-04-20
Identifier: fgcu_ir_000706
Format: Document (PDF)

Title: Best Practices in Undergraduate Clinical Laboratory Science Online Education and Effective Use of Educational Technology Tools.
Creator: Zemplinski, Julie
Abstract / Description: This article discusses the best practices of course design and successful delivery of online clinical laboratory science (CLS) courses, and informs educators about the effective use of currently available educational technology tools used to increase student engagement.
Date Issued: 2012-10-01
Identifier: fgcu_ir_000733
Format: Citation

Title: A Review of Medical Errors in Laboratory Diagnostics and Where We Are Today.
Creator: Zemplinski, Julie
Abstract / Description: While many areas of health care are still struggling with the issue of patient safety, laboratory diagnostics has always been a forerunner in pursuing this issue. Significant progress has been made since the release of “To Err is Human.”1 This article briefly reviews laboratory quality assessment and looks at recent statistics concerning laboratory errors.
Date Issued: 2012-02-01
Identifier: fgcu_ir_000734
Format: Citation

Title: It Takes a Community to Resurrect a CLS Program.
Creator: Zemplinski, Julie, Van Der Heyden, Brenda
Abstract / Description: Florida Gulf Coast University (FGCU) revised and reactivated its former 2+2 NAACLS accredited program in 2006, by instituting an innovative 3 + 1 approach. With the efforts of the community laboratories, FGCU instituted an innovative structure which made its CLS program more viable by greatly reducing expenses of operation without sacrificing the quality of education.
Date Issued: 2011-10-01
Identifier: fgcu_ir_000735
Format: Citation

Title: Workplace Lactation Programs in Small WIC Service Sites: A Potential Model.
Creator: Angeletti, Michelle A., Llossas, Jose R.
Abstract / Description: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) has an opportunity to protect, promote, and support breastfeeding by implementing and modeling workplace lactation programs in small WIC agencies that may have barriers regarding the lack of both human and financial resources. The goal of this article was to describe effective strategies for agency administrators in small WIC service sites so that they can reduce barriers, successfully implement workplace...
Show moreThe Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) has an opportunity to protect, promote, and support breastfeeding by implementing and modeling workplace lactation programs in small WIC agencies that may have barriers regarding the lack of both human and financial resources. The goal of this article was to describe effective strategies for agency administrators in small WIC service sites so that they can reduce barriers, successfully implement workplace lactation policies and programs, and model successful strategies for other small employers.
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Date Issued: 2017-11-17
Identifier: 10.1016/j.jneb.2017.10.001, fgcu_ir_001000, https://linkinghub.elsevier.com/retrieve/pii/S1499404617309508
Format: Citation

Title: Association of HLA-DRB1 genetic variants with the persistence of atopic dermatitis.
Creator: Gupta, Jayanta, Margolis, David J., Mitra, Nandita, Kim, Brian, Hoffstad, Ole, Papadopoulos, Maryte, Wubbenhorst, Bradley, Nathanson, Katherine L., Duke, Jamie L., Monos,...
Show moreGupta, Jayanta, Margolis, David J., Mitra, Nandita, Kim, Brian, Hoffstad, Ole, Papadopoulos, Maryte, Wubbenhorst, Bradley, Nathanson, Katherine L., Duke, Jamie L., Monos, Dimitri, Kamoun, Malek
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Abstract / Description: Atopic dermatitis (AD) is a waxing and waning illness of childhood that is likely caused by interactions between an altered skin barrier and immune dysregulation. The goal of our study was to evaluate the association of DRB1 genetic variants and the persistence of AD using whole exome sequencing and high resolution typing. DRB1 was interrogated based on previous reports that utilized high throughput techniques. We evaluated an ongoing nation-wide long-term cohort of children with AD in which...
Show moreAtopic dermatitis (AD) is a waxing and waning illness of childhood that is likely caused by interactions between an altered skin barrier and immune dysregulation. The goal of our study was to evaluate the association of DRB1 genetic variants and the persistence of AD using whole exome sequencing and high resolution typing. DRB1 was interrogated based on previous reports that utilized high throughput techniques. We evaluated an ongoing nation-wide long-term cohort of children with AD in which patients are asked every 6 months about their medication use and their AD symptoms. In total, 87 African-American and 50 European-American children were evaluated. Genetic association analysis was performed using a software tool focusing on amino acid variable positions shared by HLA-DRB1 alleles covering the antigen presenting domain. Amino acid variations at position 9 (pocket 9), position 26, and position 78 (pocket 4) were marginally associated with the prevalence of AD. However, the odds ratio was 0.30 (0.14, 0.68; p = 0.003) for residue 78, 0.27 (0.10, 0.69; p = 0.006) for residue 26 and not significant for residue 9 with respect to the persistence of AD. In conclusion, amino acid variations at peptide-binding pockets of HLA-DRB1 were associated with the persistence of AD in African-American children.
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Date Issued: 2015-08-01
Identifier: fgcu_ir_000717
Format: Citation

Title: Lack of Effectiveness of Hyperbaric Oxygen Therapy for the Treatment of Diabetic Foot Ulcer and the Prevention of Amputation.
Creator: Gupta, Jayanta, Margolis, David J., Hoffstad, Ole, Papadopoulos, Maryte, Glick, Henry, Thom, Stephen R., Mitra, Nandita
Abstract / Description: Hyperbaric oxygen (HBO) is a device that is used to treat foot ulcers. The study goal was to compare the effectiveness of HBO with other conventional therapies administered in a wound care network for the treatment of a diabetic foot ulcer and prevention of lower-extremity amputation. This was a longitudinal observational cohort study. To address treatment selection bias, we used propensity scores to determine the "propensity" that an individual was selected to receive HBO. We studied 6,259...
Show moreHyperbaric oxygen (HBO) is a device that is used to treat foot ulcers. The study goal was to compare the effectiveness of HBO with other conventional therapies administered in a wound care network for the treatment of a diabetic foot ulcer and prevention of lower-extremity amputation. This was a longitudinal observational cohort study. To address treatment selection bias, we used propensity scores to determine the "propensity" that an individual was selected to receive HBO. We studied 6,259 individuals with diabetes, adequate lower limb arterial perfusion, and foot ulcer extending through the dermis, representing 767,060 person-days of wound care. In the propensity score-adjusted models, individuals receiving HBO were less likely to have healing of their foot ulcer (hazard ratio 0.68 [95% CI 0.63-0.73]) and more likely to have an amputation (2.37 [1.84-3.04]). Additional analyses, including the use of an instrumental variable, were conducted to assess the robustness of our results to unmeasured confounding. HBO was not found to improve the likelihood that a wound might heal or to decrease the likelihood of amputation in any of these analyses. Use of HBO neither improved the likelihood that a wound would heal nor prevented amputation in a cohort of patients defined by Centers for Medicare and Medicaid Services eligibility criteria. The usefulness of HBO in the treatment of diabetic foot ulcers needs to be reevaluated.
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Date Issued: 2013-07-01
Identifier: fgcu_ir_000719
Format: Citation

Title: Resolving the etiology of atopic disorders by using genetic analysis of racial ancestry.
Creator: Gupta, Jayanta, Johansson, Elisabet, Bernstein, Jonathan A, Chakraborty, Ranajit, Khurana Hershey, Gurjit K, Rothenberg, Marc E., Mersha, Tesfaye B
Abstract / Description: Atopic dermatitis (AD), food allergy, allergic rhinitis, and asthma are common atopic disorders of complex etiology. The frequently observed atopic march from early AD to asthma, allergic rhinitis, or both later in life and the extensive comorbidity of atopic disorders suggest common causal mechanisms in addition to distinct ones. Indeed, both disease-specific and shared genomic regions exist for atopic disorders. Their prevalence also varies among races; for example, AD and asthma have a...
Show moreAtopic dermatitis (AD), food allergy, allergic rhinitis, and asthma are common atopic disorders of complex etiology. The frequently observed atopic march from early AD to asthma, allergic rhinitis, or both later in life and the extensive comorbidity of atopic disorders suggest common causal mechanisms in addition to distinct ones. Indeed, both disease-specific and shared genomic regions exist for atopic disorders. Their prevalence also varies among races; for example, AD and asthma have a higher prevalence in African Americans when compared with European Americans. Whether this disparity stems from true genetic or race-specific environmental risk factors or both is unknown. Thus far, the majority of the genetic studies on atopic diseases have used populations of European ancestry, limiting their generalizability. Large-cohort initiatives and new analytic methods, such as admixture mapping, are currently being used to address this knowledge gap. Here we discuss the unique and shared genetic risk factors for atopic disorders in the context of ancestry variations and the promise of high-throughput "-omics"-based systems biology approach in providing greater insight to deconstruct their genetic and nongenetic etiologies. Future research will also focus on deep phenotyping and genotyping of diverse racial ancestry, gene-environment, and gene-gene interactions.
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Date Issued: 2016-09-01
Identifier: fgcu_ir_000699
Format: Citation

Title: Thymic Stromal Lymphopoietin Variation, Filaggrin Loss of Function, and the Persistence of Atopic Dermatitis.
Creator: Gupta, Jayanta, Margolis, David J., Kim, Brian, Apter, Andrea J., Hoffstad, Ole, Papadopoulos, Maryte, Mitra, Nandita
Abstract / Description: Atopic dermatitis (AD) is a common chronic relapsing inflammatory disease of the skin that is seen most often in childhood. The development of AD has been associated with genetic polymorphisms, skin barrier dysfunction, environmental exposures, and host immune dysregulation. Conceptually, the pathophysiology of AD may be associated with a child’s sensitization to specific environmental or food allergens in association with Quiz Ref IDskin barrier dysfunction, which is hypothesized to result...
Show moreAtopic dermatitis (AD) is a common chronic relapsing inflammatory disease of the skin that is seen most often in childhood. The development of AD has been associated with genetic polymorphisms, skin barrier dysfunction, environmental exposures, and host immune dysregulation. Conceptually, the pathophysiology of AD may be associated with a child’s sensitization to specific environmental or food allergens in association with Quiz Ref IDskin barrier dysfunction, which is hypothesized to result from defects in the production of filaggrin (FLG) protein, a key constituent of the granular cell layer.3 In 2006, loss-of-function mutations in the FLG gene (OMIM 135940) were shown to be associated with AD. Ultimately, FLG proteolysis results in the creation of natural moisturizing factors that are part of the skin barrier. Animal models have shown that a defect in the production of FLG creates a more porous skin surface, resulting in epicutaneous sensitization to environmental allergens and activating the host immune system, thereby resulting in local inflammation, pruritus, and visible skin lesions.
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Date Issued: 2014-03-01
Identifier: fgcu_ir_000718
Format: Citation

Title: Genome-Wide Association of CKD Progression: The Chronic Renal Insufficiency Cohort Study.
Creator: Gupta, Jayanta, Parsa, Afshin, Salimi, Shabnam, Kanetsky, Peter A., Xiao, Rui, Mitra, Nandita, Limou, Sophie, Xie, Dawei, Anderson, Amanda Hyre, Ojo, Akinlolu, Kusek, John W.,...
Show moreGupta, Jayanta, Parsa, Afshin, Salimi, Shabnam, Kanetsky, Peter A., Xiao, Rui, Mitra, Nandita, Limou, Sophie, Xie, Dawei, Anderson, Amanda Hyre, Ojo, Akinlolu, Kusek, John W., Lora, Claudia M., Hamm, L. Lee, He, Jiang, Sandholm, Niina, Jeff, Janina, Raj, Dominic E., Böger, Carsten A., Bottinger, Erwin
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Abstract / Description: The rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome–wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD. We stratified all analyses by race and subsequently, diabetes status. Single-nucleotide polymorphisms ...
Show moreThe rate of decline of renal function varies significantly among individuals with CKD. To understand better the contribution of genetics to CKD progression, we performed a genome–wide association study among participants in the Chronic Renal Insufficiency Cohort Study. Our outcome of interest was CKD progression measured as change in eGFR over time among 1331 blacks and 1476 whites with CKD. We stratified all analyses by race and subsequently, diabetes status. Single-nucleotide polymorphisms (SNPs) that surpassed a significance threshold of P<1×10−6 for association with eGFR slope were selected as candidates for follow-up and secondarily tested for association with proteinuria and time to ESRD. We identified 12 such SNPs among black patients and six such SNPs among white patients. We were able to conduct follow-up analyses of three candidate SNPs in similar (replication) cohorts and eight candidate SNPs in phenotype-related (validation) cohorts. Among blacks without diabetes, rs653747 in LINC00923 replicated in the African American Study of Kidney Disease and Hypertension cohort (discovery P=5.42×10−7; replication P=0.039; combined P=7.42×10−9). This SNP also associated with ESRD (hazard ratio, 2.0 (95% confidence interval, 1.5 to 2.7); P=4.90×10−6). Similarly, rs931891 in LINC00923 associated with eGFR decline (P=1.44×10−4) in white patients without diabetes. In summary, SNPs in LINC00923, an RNA gene expressed in the kidney, significantly associated with CKD progression in individuals with nondiabetic CKD. However, the lack of equivalent cohorts hampered replication for most discovery loci. Further replication of our findings in comparable study populations is warranted.
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Date Issued: 2017-03-01
Identifier: fgcu_ir_000713
Format: Citation

Title: Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D‐Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes.
Creator: Gupta, Jayanta, Denburg, Michelle R., Hoofnagle, Andrew N., Sayed, Samir, Boer, Ian H., Appel, Lawrence J., Durazo-Arvizu, Ramon, Whitehead, Krista, Feldman, Harold I., Leonard,...
Show moreGupta, Jayanta, Denburg, Michelle R., Hoofnagle, Andrew N., Sayed, Samir, Boer, Ian H., Appel, Lawrence J., Durazo-Arvizu, Ramon, Whitehead, Krista, Feldman, Harold I., Leonard, Mary B.
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Abstract / Description: Studies using vitamin D‐binding protein (DBP) concentrations to estimate free and bioavailable vitamin D have increased dramatically in recent years. Combinations of two single‐nucleotide polymorphisms (SNPs) produce three major DBP isoforms (Gc1f, Gc1s, and Gc2). A recent study showed that DBP concentrations quantified by liquid chromatography–tandem mass spectrometry (LC‐MS/MS) did not differ by race, whereas a widely used monoclonal enzyme‐linked immunosorbent assay (ELISA) quantified DBP...
Show moreStudies using vitamin D‐binding protein (DBP) concentrations to estimate free and bioavailable vitamin D have increased dramatically in recent years. Combinations of two single‐nucleotide polymorphisms (SNPs) produce three major DBP isoforms (Gc1f, Gc1s, and Gc2). A recent study showed that DBP concentrations quantified by liquid chromatography–tandem mass spectrometry (LC‐MS/MS) did not differ by race, whereas a widely used monoclonal enzyme‐linked immunosorbent assay (ELISA) quantified DBP differentially by isoform, yielding significantly lower DBP concentrations in black versus white individuals. We compared measurements of serum DBP using a monoclonal ELISA, a polyclonal ELISA, and LC‐MS/MS in 125 participants in the Chronic Renal Insufficiency Cohort (CRIC). Serum free and bioavailable 25OHD were calculated based on DBP concentrations from these three assays in homozygous participants, and race differences were compared. We confirmed that the monoclonal ELISA quantifies DBP differentially by isoform and showed that the polyclonal ELISA is not subject to this bias. Whereas ≤9% of the variability in DBP concentrations quantified using either LC‐MS/MS or the polyclonal ELISA was explained by genotype, 85% of the variability in the monoclonal ELISA‐based measures was explained by genotype. DBP concentrations measured by the monoclonal ELISA were disproportionately lower than LC‐MS/MS‐based results for Gc1f homozygotes (median difference –67%; interquartile range [IQR] –71%, –64%), 95% of whom were black. In contrast, the polyclonal ELISA yielded consistently and similarly higher measurements of DBP than LC‐MS/MS, irrespective of genotype, with a median percent difference of +50% (IQR +33%, +65%). Contrary to findings using the monoclonal ELISA, DBP concentrations did not differ by race, and free and bioavailable 25OHD were significantly lower in black versus white participants based on both the polyclonal ELISA and LC‐MS/MS, consistent with their lower total 25OHD. Future studies of DBP and free or bioavailable vitamin D metabolites should employ DBP assays that are not biased by DBP genotype. © 2016 American Society for Bone and Mineral Research.
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Date Issued: 2016-03-08
Identifier: fgcu_ir_000715
Format: Citation

Title: Inflammation and Progression of CKD: The CRIC Study.
Creator: Gupta, Jayanta, Amdur, Richard L., Feldman, Harold I., Yang, Wei, Kanetsky, Peter, Shlipak, Michael, Rahman, Mahboob, Lash, James P., Townsend, Raymond, Ojo, Akinlolu, Roy...
Show moreGupta, Jayanta, Amdur, Richard L., Feldman, Harold I., Yang, Wei, Kanetsky, Peter, Shlipak, Michael, Rahman, Mahboob, Lash, James P., Townsend, Raymond, Ojo, Akinlolu, Roy-Chaudhury, Ashay, Go, Alan S., Joffe, Marshall, He, Jiang, Balakrishnan, Vaidyanathapuram S., Kimmel, Paul L., Kusek, John W., Raj, Dominic E.
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Abstract / Description: CKD is a global public health problem with significant mortality and morbidity. We examined the multivariable association of plasma levels of IL-1, IL-1 receptor antagonist, IL-6, TNF-α, TGF-β, high–sensitivity C–reactive protein, fibrinogen, and serum albumin with progression of CKD in 3430 Chronic Renal Insufficiency Cohort study participants.
Date Issued: 2016-09-07
Identifier: fgcu_ir_000714
Format: Citation

Title: Variants in genes belonging to the fibroblast growth factor family are associated with lower extremity amputation in non-Hispanic whites: Findings from the chronic renal insufficiency cohort study.
Creator: Gupta, Jayanta, Mitra, Nandita, Townsend, Raymond R., Fischer, Michael, Schelling, Jeffrey R., Margolis, David J.
Abstract / Description: Diabetes is the major risk factor for nontraumatic lower extremity amputation (LEA). The role of genetic polymorphisms in predisposing diabetics to impaired wound healing leading to LEA has not been sufficiently explored. We investigated the association between a set of genes belonging to the angiogenesis/wound repair pathway with LEA in the Chronic Renal Insufficiency Cohort, a study of adults with chronic kidney disease (CKD) that includes a subgroup with diabetes. This study was performed...
Show moreDiabetes is the major risk factor for nontraumatic lower extremity amputation (LEA). The role of genetic polymorphisms in predisposing diabetics to impaired wound healing leading to LEA has not been sufficiently explored. We investigated the association between a set of genes belonging to the angiogenesis/wound repair pathway with LEA in the Chronic Renal Insufficiency Cohort, a study of adults with chronic kidney disease (CKD) that includes a subgroup with diabetes. This study was performed on 3,772 Chronic Renal Insufficiency Cohort participants who were genotyped on the ITMAT-Broad-CARe array chip. A total of 1,017 single-nucleotide polymorphisms (SNPs) in 22 genes belonging to the angiogenesis/would repair pathway were investigated. LEA was determined from patient self-report. The association between genetic variants and LEA status was examined using logistic regression and additive genetic models after stratifying the cohort by race/ethnicity and diabetic status. Unadjusted analyses as well as analyses adjusted for age, sex, estimated glomerular filtration rate, body mass index, peripheral vascular disease, hemoglobin A1c, and population stratification were performed. In non-Hispanic white participants with diabetes, rs11938826 and rs1960669, both intronic SNPs in the gene basic fibroblast growth factor-2 (FGF2), were significantly associated with LEA in covariate-adjusted analysis (OR: 2.83 (95% CI: 1.73, 4.62); p-value: 0.000034; Bonferroni adjusted p-value: 0.0006) and (OR: 2.61 (95% CI: 1.48, 4.61); p-value: 0.00095; Bonferroni adjusted p-value: 0.02). In the same subgroup, rs10883688, an FGF8 SNP of unknown functional effect, was also associated with LEA (OR: 1.72 (95% Confidence Interval: 1.14, 2.6); p-value: 0.00999; Bonferroni adjusted p-value: 0.04). No statistically significant associations were identified in the other ethnic groups. In conclusion, variant/s in FGF2 and FGF8 may predispose diabetics with CKD to LEA. Dysregulation of the FGF2 gene represents an opportunity to understand further, and possibly intervene upon, mechanisms of wound healing in diabetics with CKD.
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Date Issued: 2016-07-01
Identifier: fgcu_ir_000700
Format: Citation

Title: Replication of genome-wide association study ( GWAS) susceptibility loci in a Latino bipolar disorder cohort.
Creator: Gupta, Jayanta, Gonzalez, Suzanne, Villa, Erika, Mallawaarachchi, Indika, Rodriguez, Marco, Ramirez, Mercedes, Zavala, Juan, Armas, Regina, Dassori, Albana, Contreras, Javier,...
Show moreGupta, Jayanta, Gonzalez, Suzanne, Villa, Erika, Mallawaarachchi, Indika, Rodriguez, Marco, Ramirez, Mercedes, Zavala, Juan, Armas, Regina, Dassori, Albana, Contreras, Javier, Flores, Deborah, Jerez, Alvaro, Ontiveros, Alfonso, Nicolini, Humberto, Escamilla, Michael
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Abstract / Description: Recent genome-wide association studies ( GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder ( BD) and/or schizophrenia ( SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms ( SNPs) in a sample of...
Show moreRecent genome-wide association studies ( GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder ( BD) and/or schizophrenia ( SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms ( SNPs) in a sample of Latino subjects with BD. Methods A total of 2254 Latino individuals were genotyped for 91 SNPs identified in previous BD and/or SC GWASs, along with selected SNPs in strong linkage disequilibrium with these markers. Family-based single marker and haplotype association testing was performed using the PBAT software package. Empirical P-values were derived from 10 000 permutations. Results Associations of eight a priori GWAS SNPs with BD were replicated with nominal ( P≤.05) levels of significance. These included SNPs within nuclear factor I A ( NFIA), serologically defined colon cancer antigen 8 ( SDCCAG8), lysosomal associated membrane protein 3 ( LAMP3), nuclear factor kappa B subunit 1 ( NFKB1), major histocompatibility complex, class I, B ( HLA-B) and 5′-nucleotidase, cytosolic II ( NT5C2) and SNPs within intragenic regions microRNA 6828 ( MIR6828) -solute carrier family 7 member 14 ( SLC7A14) and sonic hedgehog ( SHH) -long intergenic non-protein coding RNA 1006 ( LINC01006). Of the 76 ancestral haploblocks that were tested for associations with BD, our top associated haploblock was located in LAMP3; however, the association did not meet statistical thresholds of significance following Bonferroni correction. Conclusions These results indicate that some of the gene variants found to be associated with BD or SC in other populations are also associated with BD risk in Latinos. Variants in six genes and two intragenic regions were associated with BD in our Latino sample and provide additional evidence for overlap in genetic risk between SC and BD.
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Date Issued: 2016-09-01
Identifier: fgcu_ir_000712
Format: Citation

Title: Genome-wide association studies in pediatric chronic kidney disease.
Creator: Gupta, Jayanta, Kanetsky, Peter, Wuttke, Matthias, Köttgen, Anna, Schaefer, Franz, Wong, Craig
Abstract / Description: The genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a...
Show moreThe genome-wide association study (GWAS) has become an established scientific method that provides an unbiased screen for genetic loci potentially associated with phenotypes of clinical interest, such as chronic kidney disease (CKD). Thus, GWAS provides opportunities to gain new perspectives regarding the genetic architecture of CKD progression by identifying new candidate genes and targets for intervention. As such, it has become an important arm of translational science providing a complementary line of investigation to identify novel therapeutics to treat CKD. In this review, we describe the method and the challenges of performing GWAS in the pediatric CKD population. We also provide an overview of successful GWAS for kidney disease, and we discuss the established pediatric CKD cohorts in North America and Europe that are poised to identify genetic risk variants associated with CKD progression.
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Date Issued: 2016-08-01
Identifier: fgcu_ir_000701
Format: Citation

Title: Reliability and validity of genotyping filaggrin null mutations.
Creator: Gupta, Jayanta, Margolis, David J., Apter, Andrea J., Mitra, Nandita, Hoffstad, Ole, Papadopoulos, Maryte, Rebbeck, Tim R., MacCallum, Stephanie, Campbell, Linda E., Sandilands,...
Show moreGupta, Jayanta, Margolis, David J., Apter, Andrea J., Mitra, Nandita, Hoffstad, Ole, Papadopoulos, Maryte, Rebbeck, Tim R., MacCallum, Stephanie, Campbell, Linda E., Sandilands, Aileen, McLean, W.H. Irwin
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Abstract / Description: Atopic dermatitis (AD) is a common chronic waxing and waning disease. Of those with AD and European or Asian ancestry, more than 20% will have a FLG loss of function mutation (FLG null) resulting in the absence or near absence of filaggrin protein in the stratum corneum. It has been suggested that FLG null genetic testing might be a helpful clinical tool. The FLG gene is difficult to sequence because of its large, redundant, and repetitive structure limiting the availability of specific...
Show moreAtopic dermatitis (AD) is a common chronic waxing and waning disease. Of those with AD and European or Asian ancestry, more than 20% will have a FLG loss of function mutation (FLG null) resulting in the absence or near absence of filaggrin protein in the stratum corneum. It has been suggested that FLG null genetic testing might be a helpful clinical tool. The FLG gene is difficult to sequence because of its large, redundant, and repetitive structure limiting the availability of specific primer binding sites for PCR amplification. There are several techniques that are commonly used for genetic testing including the more time intensive TaqMan® allelic discrimination assays and high-throughput methods that utilize beadchip technology. The goal of this study was to compare the reliability (the consistency of and ability to replicate a measurement) and validity (the ability of a measurement to identify the correct event) of these two techniques.
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Date Issued: 2013-04-01
Identifier: fgcu_ir_000720
Format: Citation

Atopic dermatitis. (9)	+ -
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Asthma. (5)	+ -
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Albuminuria. (1)	+ -
Allelopathy. (1)	+ -
Allergens. (1)	+ -
Allergic rhinitis (1)	+ -
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Interleukin-6. (1)	+ -

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Renal Insufficiency, Chronic. (1)	+ -

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