title: 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.
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.
authors.affiliation: Department of Epidemiology, the Johns Hopkins University School of Hygiene and Public Health, 615 N. Wolfe Street, Room W6513, Baltimore, MD 21205, USA. wkao@jhsph.edu
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Molly S
authors.initials: MS
authors.lastname: Bray
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Brancati
mesh_terms: D019943:Amino Acid Substitution; D001161:Arteriosclerosis / Q000453:epidemiology*; D044383:Black People / Q000235:genetics*; D001824:Body Constitution; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000235:genetics; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors