Common Polymorphisms in the Adiponectin Gene ACDC Are Not Associated With Diabetes in Pima Indians.
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.
Vozarova de Courten
Barbora
B
Translational Genomics Research Institute, Diabetes Research Unit, NIDDK, NIH, 400 North 5th St., Phoenix, Arizona, USA.
Hanson
Robert L
RL
Funahashi
Tohru
T
Lindsay
Robert S
RS
Matsuzawa
Yuji
Y
Tanaka
Sachiyo
S
Thameem
Farook
F
Gruber
Jonathan D
JD
Froguel
Philippe
P
Wolford
Johanna K
JK
D052242:Adiponectin; D001130:Arizona / Q000453:epidemiology; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics*; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood; D008137:Longitudinal Studies; D009765:Obesity / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids