TY - JOUR

T1 - Common Polymorphisms in the Adiponectin Gene ACDC Are Not Associated With Diabetes in Pima Indians

AU - de Courten, Barbora

AU - Hanson, Robert L

AU - Funahashi, Tohru

AU - Lindsay, Robert S

AU - Matsuzawa, Yuji

AU - Tanaka, Sachiyo

AU - Thameem, Farook

AU - Gruber, Jonathan D

AU - Froguel, Philippe

AU - Wolford, Johanna K

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Adiponectin is an abundant adipose tissue-derived protein with important metabolic effects. Plasma adiponectin levels are decreased in obese individuals, and low adiponectin levels predict insulin resistance and type 2 diabetes. Two variants in the adiponectin gene ACDC have been previously associated with plasma adiponectin levels, obesity, insulin resistance, and type 2 diabetes. To determine the role of genetic variation in ACDC in susceptibility to obesity and type 2 diabetes in Pima Indians, we screened the promoter, exons, and exon-intron boundaries of the gene to identify allelic variants. We identified 17 informative polymorphisms that comprised four common (minor allele frequency >15%) linkage disequilibrium clusters consisting of 1-4 variants each. We genotyped one representative polymorphism from each cluster in 1,338 individuals and assessed genotypic association with type 2 diabetes, BMI, serum lipid levels, serum adiponectin levels, and measures of insulin sensitivity and secretion. None of the ACDC variants were associated with type 2 diabetes, BMI, or measures of insulin sensitivity or secretion. One variant, single nucleotide polymorphism (SNP)-12823, was associated with serum adiponectin levels (P = 0.002), but this association explained only 2% of the variance of serum adiponectin levels. Our findings suggest that these common ACDC polymorphisms do not play a major role in susceptibility to obesity or type 2 diabetes in this population.

AB - Adiponectin is an abundant adipose tissue-derived protein with important metabolic effects. Plasma adiponectin levels are decreased in obese individuals, and low adiponectin levels predict insulin resistance and type 2 diabetes. Two variants in the adiponectin gene ACDC have been previously associated with plasma adiponectin levels, obesity, insulin resistance, and type 2 diabetes. To determine the role of genetic variation in ACDC in susceptibility to obesity and type 2 diabetes in Pima Indians, we screened the promoter, exons, and exon-intron boundaries of the gene to identify allelic variants. We identified 17 informative polymorphisms that comprised four common (minor allele frequency >15%) linkage disequilibrium clusters consisting of 1-4 variants each. We genotyped one representative polymorphism from each cluster in 1,338 individuals and assessed genotypic association with type 2 diabetes, BMI, serum lipid levels, serum adiponectin levels, and measures of insulin sensitivity and secretion. None of the ACDC variants were associated with type 2 diabetes, BMI, or measures of insulin sensitivity or secretion. One variant, single nucleotide polymorphism (SNP)-12823, was associated with serum adiponectin levels (P = 0.002), but this association explained only 2% of the variance of serum adiponectin levels. Our findings suggest that these common ACDC polymorphisms do not play a major role in susceptibility to obesity or type 2 diabetes in this population.

KW - Adiponectin

KW - Arizona

KW - Body Mass Index

KW - Diabetes Mellitus, Type 2

KW - Genotype

KW - Humans

KW - Indians, North American

KW - Intercellular Signaling Peptides and Proteins

KW - Linkage Disequilibrium

KW - Lipids

KW - Longitudinal Studies

KW - Obesity

KW - Pedigree

KW - Polymorphism, Genetic

KW - Polymorphism, Single Nucleotide

KW - Prevalence

M3 - Journal article

C2 - 15616040

VL - 54

SP - 284

EP - 289

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 1

ER -