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Pro12Ala of the peroxisome proliferator-activated receptor-gamma2 gene is associated with lower serum insulin levels in nonobese African Americans: the Atherosclerosis Risk in Communities Study.

TitlePro12Ala of the peroxisome proliferator-activated receptor-gamma2 gene is associated with lower serum insulin levels in nonobese African Americans: the Atherosclerosis Risk in Communities Study.
Publication TypeJournal Article
Year of Publication2003
AuthorsKao LWH, Coresh J, Shuldiner AR, Boerwinkle E, Bray MS, Brancati FL
Corporate AuthorsAtherosclerosis Risk in Communities Study
JournalDiabetes
Volume52
Issue6
Pagination1568-72
Date Published2003 Jun
ISSN0012-1797
KeywordsAmino Acid Substitution, Arteriosclerosis, Blacks, Body Constitution, Body Mass Index, Cardiovascular Diseases, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Gene Frequency, Genetic Variation, Genotype, Humans, Insulin, Receptors, Cytoplasmic and Nuclear, Transcription Factors, United States, Whites
Abstract

Recent research suggests that the Pro12Ala variant in peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with diabetes- and obesity-related traits, and that its effects may be modified by obesity status. We characterized this variant in a population-based sample of 1,441 middle-aged African-American individuals with respect to diabetes-, obesity-, and other cardiovascular-related traits, both cross-sectionally and prospectively. The overall frequency of Ala12 was 1.9% (95% CI 1.5-2.5%), significantly lower than in Caucasian populations. Consistent with previous findings in Caucasians, African Americans with type 2 diabetes tended to be less likely to have the Pro/Ala genotype than those without (odds ratio [OR] 0.64, 95% CI 0.34-1.20); however, this OR was not statistically significant. Among nonobese individuals, the Pro/Ala genotype was associated with significantly lower ln(insulin) (P = 0.001), lower ln(HOMA-IR) (homeostasis model assessment of insulin resistance) (P = 0.002), higher fasting glucose-to-insulin ratio (P = 0.005), and lower diastolic blood pressure (P = 0.02). Among overweight individuals (BMI 25-29.9 kg/m(2)), the Pro/Ala genotype was associated with greater BMI (P = 0.02), waist-to-hip ratio (P = 0.01), and waist circumference (P = 0.04). Among obese individuals, there was no association between any of the diabetes- or obesity-related traits and the Pro12Ala PPAR-gamma2 variant. We conclude that among nonobese African Americans, the Pro/Ala genotype is associated with markers of greater insulin sensitivity.

DOI10.2337/diabetes.52.6.1568
Alternate JournalDiabetes
PubMed ID12765972
Grant List1K24 DK 6222-01 / DK / NIDDK NIH HHS / United States
1R01 DK 53959-01 / DK / NIDDK NIH HHS / United States
K24 DK 02673 / DK / NIDDK NIH HHS / United States
N01 HC 55015 / HC / NHLBI NIH HHS / United States
N01 HC 55016 / HC / NHLBI NIH HHS / United States
N01 HC 55018 / HC / NHLBI NIH HHS / United States
N01 HC 55019 / HC / NHLBI NIH HHS / United States
N01 HC 55020 / HC / NHLBI NIH HHS / United States
N01 HC 55021 / HC / NHLBI NIH HHS / United States
N01 HC 55022 / HC / NHLBI NIH HHS / United States
T32 HL 07024-23 / HL / NHLBI NIH HHS / United States