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Diabetes Publish Ahead of Print published online ahead of print April 6, 2007
DOI: 10.2337/db06-1447
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Original Research

Variations in adiponectin receptor genes and susceptibility to type 2 diabetes in women: A tagging-SNP haplotype analysis

Lu Qi1,3, Alessandro Doria4, Elena Giorgi5, and Frank B. Hu1,2,3

1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
2Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
3Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
4Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts
5Department of Mathematics and Statistics, University of Massachusetts, Amherst, Massachusetts

Correspondence: nhlqi{at}channing.harvard.edu

Adiponectin has been associated with low diabetes risk. The metabolic effects of adiponectin are mediated by adiponectin receptor 1 (ADIPOR1) and receptor 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 sixteen 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% (OR=0.76, 95%CI 0.61-0.96, and P=0.02) decreased risk compared with the most common haplotype 110000, adjusting for age, BMI, and other covariates. A 3' UTR polymorphism, rs1139646, showed the strongest and nominally significant association with greater diabetic risk (unadjusted OR=1.26, 95%CI 1.03-1.53; and adjusted OR=1.36, 95%CI 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 permutation). 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.


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