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Diabetes 55:1512-1516, 2006
DOI: 10.2337/db05-1520
© 2006 by the American Diabetes Association
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Adiponectin Genetic Variability, Plasma Adiponectin, and Cardiovascular Risk in Patients With Type 2 Diabetes

Lu Qi1,2, Alessandro Doria3, JoAnn E. Manson2,4,5, James B. Meigs6, David Hunter1,2,4, Christos S. Mantzoros7, and Frank B. Hu1,2,4

1 Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
2 Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
3 Research Division, Department of Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
4 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
5 Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
6 General Internal Medicine and Clinical Epidemiology Units, General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
7 Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

Address correspondence and reprint requests to Dr. Lu Qi, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115. E-mail nhlqi{at}channing.harvard.edu

Abbreviations: CVD, cardiovascular disease; LD, linkage disequilibrium; SNP, single nucleotide polymorphism

Adiponectin is an adipocyte-derived hormone that has shown anti-inflammatory and antiatherogenic effects. We assessed the associations of variants in the adiponectin gene (ADIPOQ) with circulating adiponectin levels and cardiovascular risk among women with type 2 diabetes. Of 989 diabetic women from the Nurses’ Health Study, 285 developed cardiovascular disease (CVD) during follow-up through 2000. We genotyped five ADIPOQ polymorphisms in the CVD case and control subjects. A promoter polymorphism –11365C->G was significantly associated with lower plasma adiponectin levels (P = 0.004). The homozygotes of allele –4034C were significantly associated with ~60% increased cardiovascular risk (odds ratio 1.62 [95% CI 1.07–2.45]). Adjustment for age, BMI, and other covariates did not appreciably change the associations. In addition, a common haplotype possessing allele +276T (CAATT) was associated with a significantly lower CVD risk than the most common haplotype (CAATG) (0.70 [0.50–0.98]). In our meta-analysis of 827 CVD case and 1,887 CVD-free control subjects, polymorphism +276G->T was significantly associated with ~45% (20–62%) decreased CVD risk under a recessive inheritance mode in diabetic patients. In conclusion, ADIPOQ promoter polymorphism –11365C->G was associated with plasma adiponectin levels, whereas polymorphisms –4034A->C and +276G->T were associated with CVD risk in diabetic patients.


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Copyright © 2006 by the American Diabetes Association.