Dataset Information

Lack of interaction of beta-cell-function-associated variants with hypertension on change in fasting glucose and diabetes risk: the Framingham Offspring Study.

ABSTRACT: To test whether pancreatic beta-cell genetic frailty and hypertension (HTN) interact in their associations with change over time in fasting glucose (?FG) or type 2 diabetes mellitus (T2D) risk.We pooled data from 3471 Framingham Offspring Study participants into six ?4-year periods (15?852 person-examinations; mean age 52; 54% women). We defined two genetic exposures reflecting beta-cell genetic risk burden: single nucleotide polymorphism (SNP) score counts of fasting glucose-associated and T2D-associated risk alleles at 16 and 33 putative beta-cell loci, respectively; and three HTN exposures: HTN versus no-HTN; treated versus untreated HTN; and five mutually exclusive antihypertensive categories (beta-blockers, thiazides, renin-angiotensin system agents, combinations, others) versus untreated HTN. We tested ?4-year mean ?FG or odds of T2D by per-risk allele score change and HTN category, seeking genetic score-by-HTN interaction. Genetic scores increased ?4-year ?FG (0.6 ?mg/dl per-risk allele; P?=?8.9?×?10(-16)) and T2D-risk (?17% per-risk allele; P?=?2.1?×?10(-7)). As compared to no-HTN, HTN conferred higher ?FG (2.6 versus 1.7?mg/dl; P?

SUBMITTER: de Miguel-Yanes JM

PROVIDER: S-EPMC3745997 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Lack of interaction of beta-cell-function-associated variants with hypertension on change in fasting glucose and diabetes risk: the Framingham Offspring Study.

de Miguel-Yanes Jose M JM Porneala Bianca B Pencina Michael J MJ Fox Caroline S CS Florez Jose C JC Siscovick David S DS Dupuis Josée J Meigs James B JB

Journal of hypertension 20130501 5

<h4>Objective</h4>To test whether pancreatic beta-cell genetic frailty and hypertension (HTN) interact in their associations with change over time in fasting glucose (ΔFG) or type 2 diabetes mellitus (T2D) risk.<h4>Methods and results</h4>We pooled data from 3471 Framingham Offspring Study participants into six ∼4-year periods (15 852 person-examinations; mean age 52; 54% women). We defined two genetic exposures reflecting beta-cell genetic risk burden: single nucleotide polymorphism (SNP) score ...[more]

PMID: 23425704

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Project description:BackgroundValvular and vascular calcification are important early aging phenotypes and represent risk factors for cardiovascular morbidity and mortality. Klotho is a gene primarily expressed in the kidney that has an important role in calcium-phosphate homeostasis. The functional KL-VS variant of Klotho has been associated with aging and cardiovascular disease in human studies, but its role in valvular and vascular calcification remains unknown. We performed a candidate gene study in the Framingham Offspring Cohort to evaluate the effect of KL-VS variant of the Klotho gene on valvular calcification.MethodsWe analyzed the Klotho KL-VS genotype (rs9536314) from the Affymetrix 550K genome-wide dataset, distributed by dbGAP, on 1389 cases and 2139 controls from the Framingham Heart Study Offspring Cohort. Allele and genotype frequencies were compared between cases and controls. Valvular calcification was defined as presence of calcification on the mitral annulus or the aortic valve as determined by echocardiography. A sensitivity analysis of coronary artery calcification by electron beam computed tomography was performed on 1363 patients.ResultsThe frequency of the TT versus the TG allele was not different between the cases and the controls (39 versus 41%). The KL-VS variant of Klotho was not associated with valvular or vascular calcification, despite adequate power to detect association (86% for odds ratios ≥1.2). In sensitivity analyses, no association (P > 0.001) between other common variants of Klotho, β-Klotho or fibroblast growth factor-23 and the end points of valvular or vascular calcification was observed.ConclusionsIn our adequately powered candidate gene study, we did not observe an association with the functional KL-VS variant of Klotho and presence of valvular or vascular calcification. Future studies aimed at combining cohorts with echocardiographic phenotypes need to be conducted to identify genetic variants associated with valvular calcification.

Dataset Information

Lack of interaction of beta-cell-function-associated variants with hypertension on change in fasting glucose and diabetes risk: the Framingham Offspring Study.

Publications

Lack of interaction of beta-cell-function-associated variants with hypertension on change in fasting glucose and diabetes risk: the Framingham Offspring Study.

Similar Datasets

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