Abstract
BackgroundAlthough the peroxisome proliferator-activated receptor-γ2 (PPARG2) Pro12Ala gene variant is associated with diabetes mellitus, the associations and interactions of this polymorphism and known clinical risk factors with glycated hemoglobin (HbA1c) remain poorly understood. We investigated if carrying the Ala allele was inversely associated with HbA1c level and examined possible interactions.MethodsThis cross-sectional analysis used data collected from 1281 men and 1356 women aged 40 to 69 years who completed the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. PPARG2 polymorphism was determined by multiplex polymerase chain reaction (PCR)-based Invader assay. Multiple linear regression and ANCOVA were used to control for confounding variables (age, body mass index [BMI], energy intake, alcohol, smoking, physical activity, and family history of diabetes) and examine possible interactions.ResultsAfter adjustment, the Ala allele was significantly inversely associated with HbA1c in women but not in men. Older age, BMI, and family history of diabetes were associated with higher HbA1c in both sexes. When stratified by PPARG2 genotype, these associations were observed in subjects with the Pro12Pro genotype but not in Ala allele carriers. A significant interaction of genotype and BMI on HbA1c was observed in women. Older age, BMI, and family history of diabetes were significantly associated with high-normal HbA1c (≥5.7% NGSP), whereas PPARG2 polymorphism was not.ConclusionsAlthough PPARG2 Pro12Ala polymorphism might attenuate associations between known risk factors and HbA1c level, it had a small effect on high-normal HbA1c, as compared with clinical risk factors, in the general population.
Highlights
IntroductionThe prevalence of type 2 diabetes mellitus (type 2 diabetes) has markedly increased during the last decade
The prevalence of type 2 diabetes mellitus has markedly increased during the last decade
PPARG2 is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily,[18] and it regulates various genes involved in lipid and glucose metabolism
Summary
The prevalence of type 2 diabetes mellitus (type 2 diabetes) has markedly increased during the last decade. PPARG2 Pro12Ala Polymorphism and HbA1c in Japanese women may have diabetes.[3] Because age is an important risk factor for type 2 diabetes, the number of patients will further increase in Japan, which will result in a serious public health problem. Multiple linear regression and ANCOVA were used to control for confounding variables (age, body mass index [BMI], energy intake, alcohol, smoking, physical activity, and family history of diabetes) and examine possible interactions. BMI, and family history of diabetes were significantly associated with high-normal HbA1c (≥5.7% NGSP), whereas PPARG2 polymorphism was not. Conclusions: PPARG2 Pro12Ala polymorphism might attenuate associations between known risk factors and HbA1c level, it had a small effect on high-normal HbA1c, as compared with clinical risk factors, in the general population
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