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The longitudinal association of common susceptibility variants for type 2 diabetes and obesity with fasting glucose level and BMI.

ABSTRACT: Variation in the effects of genetic variants on physiological traits over time or with age may alter the trajectories of these traits. However, few studies have investigated this possibility for variants associated with type 2 diabetes or obesity, and these show little consensus. We aimed to characterise the possible longitudinal associations of common diabetes-susceptibility variants in the KCNJ11, PPARG, TCF7L2, IGF2BP2, CDKAL1, SLC30A8 and HHEX gene loci, with fasting glucose level; and of an obesity-associated variant in the FTO gene, with body mass index (BMI).The study analysed data from the Busselton Health Study (n = 4,554). Cross-sectional association analyses included family data and used the total association test. Longitudinal association analyses of unrelated participant data (n = 2,864) used linear mixed-effects models.In cross-sectional analyses, we observed associations of the T allele at the IGF2BP2 single nucleotide polymorphism (SNP) rs4402960 with raised fasting glucose (p = 0.045), and the A allele at the FTO SNP rs9939609 with raised BMI (p = 0.003). Longitudinal analyses showed no significant associations between SNPs and changes in fasting glucose or BMI in the same individuals, either over mean follow-up times of 18.7 and 21.8 years respectively, or with age during adulthood.There was no indication that the effects of common type 2 diabetes variants on fasting glucose varied with age during adulthood or over time.

SUBMITTER: Webster RJ

PROVIDER: S-EPMC2958899 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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The longitudinal association of common susceptibility variants for type 2 diabetes and obesity with fasting glucose level and BMI.

Webster Rebecca J RJ Warrington Nicole M NM Beilby John P JP Frayling Timothy M TM Palmer Lyle J LJ

BMC medical genetics 20101008

<h4>Background</h4>Variation in the effects of genetic variants on physiological traits over time or with age may alter the trajectories of these traits. However, few studies have investigated this possibility for variants associated with type 2 diabetes or obesity, and these show little consensus. We aimed to characterise the possible longitudinal associations of common diabetes-susceptibility variants in the KCNJ11, PPARG, TCF7L2, IGF2BP2, CDKAL1, SLC30A8 and HHEX gene loci, with fasting gluco ...[more]

PMID: 20929593

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Project description:ObjectiveTo identify long-term fasting blood glucose trajectories and to assess the association between the trajectories and the risk of arterial stiffness in individuals without diabetes.MethodsWe enrolled 16,454 non-diabetic participants from Kailuan cohort. Fasting blood glucose concentrations were measured in 2006, 2008, and 2010 survey. Brachial-ankle pulse wave velocities were measured during 2011 to 2016. Multivariate regression model was used to estimate the difference of brachial-ankle pulse wave velocity levels and logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of arterial stiffness risk, according to the fasting blood glucose trajectories.ResultsWe identified five distinct fasting blood glucose trajectories and each of the trajectories was labeled according to its range and change over 2006-2010 survey: elevated-stable pattern (5.0% of participants), elevated-decreasing pattern (6.6%), moderate-increasing pattern (10.9%), moderate-stable pattern (59.3%), and low-stable pattern (18.2%). After adjustment for potential confounders, individuals with elevated-stable pattern had a 42.6 cm/s (95%CI: 24.7 to 60.6 cm/s) higher brachial-ankle pulse wave velocity level and a 37% (OR 1.37, 95%CI: 1.14 to 1.66) higher arterial stiffness risk, and individuals with moderate-increasing pattern had a 19.6 cm/s (95%CI: 6.9 to 32.3 cm/s) higher brachial-ankle pulse wave velocity level and a 17% (OR 1.17, 95%CI: 1.03 to 1.33) higher arterial stiffness risk, related to individuals with moderate-stable pattern. We did not find significant associations of the elevated-decreasing or low-stable patterns with arterial stiffness. Consistently, the cumulative average, variability, and increased rate of fasting blood glucose during 2006-2010 survey were significantly associated with the arterial stiffness risk.ConclusionDiscrete fasting blood glucose trajectories were associated with the arterial stiffness risk in non-diabetic individuals.

Dataset Information

The longitudinal association of common susceptibility variants for type 2 diabetes and obesity with fasting glucose level and BMI.

Publications

The longitudinal association of common susceptibility variants for type 2 diabetes and obesity with fasting glucose level and BMI.

Similar Datasets

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