Adiponectin genetic variability, plasma adiponectin, and cardiovascular risk in patients with type 2 diabetes.
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 approximately 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 approximately 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.
Qi
Lu
L
Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. nhlqi@channing.harvard.edu
Doria
Alessandro
A
Manson
JoAnn E
JE
Meigs
James B
JB
Hunter
David
D
Mantzoros
Christos S
CS
Hu
Frank B
FB
D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000328:Adult; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012016:Reference Values
D052242:Adiponectin