Variations in adiponectin receptor genes and susceptibility to type 2 diabetes in women: a tagging-single nucleotide polymorphism haplotype analysis.
Adiponectin has been associated with low diabetes risk. The metabolic effects of adiponectin are mediated by adiponectin receptors 1 (ADIPOR1) and 2 (ADIPOR2). We conducted a prospective, nested case-control study of 714 cases of type 2 diabetes and 1,120 control subjects. Six polymorphisms in ADIPOR1 and 16 polymorphisms in ADIPOR2 were determined. Haplotypes inferred from ADIPOR1 polymorphisms were significantly associated with diabetes risk (overall test, -2log-likelihood = 15.1 on 5 df; P = 0.0098). A single copy of haplotype 001100 (0, common allele; and 1, minor allele) was associated with 24% decreased risk (odds ratio [OR] 0.76 [95% CI 0.61-0.96], P = 0.02) compared with the most common haplotype, 110000, adjusting for age, BMI, and other covariates. A 3' untranslated region (UTR) polymorphism, rs1139646, showed the strongest and nominally significant association with greater diabetes risk (unadjusted OR 1.26 [1.03-1.53] and adjusted OR 1.36 [1.10-1.70]). However, such an association became marginal after controlling for multiple comparisons by permutation test (P = 0.08 on the basis of 10,000 permutations). There were not significant associations between ADIPOR2 polymorphisms, individually or in haplotypes, and the risk of type 2 diabetes. In conclusion, our data indicate significant associations between ADIPOR1 haplotypes and diabetes risk but do not support a relation between ADIPOR2 variability and the disease.
Qi
Lu
L
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. nhlqi@channing.harvard.edu
Doria
Alessandro
A
Giorgi
Elena
E
Hu
Frank B
FB
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics*
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface