Human Molecular Genetics Advance Access published online on April 27, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl113
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1 Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, Massachusetts 02115; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
* To whom correspondence should be addressed. Interleukin-6 (IL-6, gene symbol IL6) is a proinflammatory cytokine. High circulating IL-6 levels have been associated with insulin resistance and greater risk of type 2 diabetes. Using a linkage disequilibrium (LD)-based approach, we sought to investigate the associations of the common polymorphisms comprehensively defining the genetic variability at the IL6 locus with diabetes risk. We conducted a case-control study of 2,691 cases of type 2 diabetes (1,692 women and 999 men) and 3,237 control subjects (2,238 women and 999 men) from the Nurses' Health Study and the Health Professional Follow-up Study. Pairwise LD analysis indicated that all the IL6 polymorphisms (rs2069827, rs1800797, rs1800795, rs1554606, rs2069849, rs2069861, and rs1818879) were in strong LD. We did not find significant associations between IL6 polymorphisms and the risk of type 2 diabetes in either women or men, individually or in haplotypes. In addition, none of the IL6 polymorphisms was significantly associated with the plasma levels of IL-6 in the control subjects. Our meta-analysis of 5,383 diabetes case and 12,069 controls indicated a null association between the best-studied 5' promoter polymorphism -174G>C (rs1800795) and diabetes risk. Diversity in adiposity, age, and sex could not account for the heterogeneity across different studies. In summary, the data in this study do not support substantial associations between the common polymorphisms in IL6 gene and circulating IL-6 levels and the risk of type 2 diabetes.
Received March 10, 2006
Revised April 21, 2006
Accepted April 21, 2006
Article
Genetic variation in IL6 gene and type 2 diabetes: Tagging-SNP haplotype analysis in large-scale case-control study and meta-analysis
Lu Qi 1 *,
Rob M. van Dam 2,
James B. Meigs 3,
JoAnn E. Manson 4,
David Hunter 5,
and
Frank B. Hu 5
2 Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
3 General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
4 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
5 Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
Lu Qi, E-mail: nhlqi{at}channing.harvard.edu
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