title: Common variations in the genes encoding C-reactive protein, tumor necrosis factor-alpha, and interleukin-6, and the risk of clinical diabetes in the Women's Health Initiative Observational Study.
abstract: BACKGROUND
  Circulating concentrations of high-sensitivity C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) have been associated with an increased risk of diabetes.
  
  
  METHODS
  To examine the roles of genetic variation in the genes encoding CRP, TNF- α, and IL-6 in the development of diabetes, we conducted a prospective case-control study nested within the Women's Health Initiative Observational Study. We followed 82 069 postmenopausal women (50-79 years of age) with no history of diabetes for incident diabetes for a mean follow-up of 5.5 years. We identified 1584 cases and matched them with 2198 controls with respect to age, ethnicity, clinical center, time of blood draw, and length of follow-up. We genotyped 13 haplotype-tagging single-nucleotide polymorphisms (tSNPs) across 2.3 kb of the CRP (C-reactive protein, pentraxin-related) gene, 16 tSNPs across 2.8 kb of the TNF (tumor necrosis factor) gene, and 14 tSNPs across 4.8 kb of the IL6 [interleukin 6 (interferon, beta 2)] gene. Plasma concentrations of TNF-α receptor 2 (TNF-α-R2) and IL-6 were measured.
  
  
  RESULTS
  After adjusting for matching factors, confounding variables, and multiple comparisons, we found 8 variants in the TNF gene to be associated with plasma TNF-α-R2 concentrations in white women (q < 0.05). After adjusting for multiple comparisons (q > 0.05), we found no association of any IL6 gene variant with plasma IL-6 concentration, nor did we find any significant associations between any SNPs among these 3 genes and diabetes risk (q > 0.05).
  
  
  CONCLUSIONS
  We found modest associations between TNF variants and circulating concentrations of TNF-α-R2. Common variants of the CRP, TNF, and IL6 genes were not significantly associated with risk of clinical diabetes in postmenopausal women.
authors.affiliation: Program on Genomics and Nutrition, Department of Epidemiology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Kei-hang K
authors.initials: KH
authors.lastname: Chan
authors.forename: Kathleen
authors.initials: K
authors.lastname: Brennan
authors.forename: Nai-chieh Y
authors.initials: NC
authors.lastname: You
authors.forename: Xuyang
authors.initials: X
authors.lastname: Lu
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Song
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.forename: Gautum
authors.initials: G
authors.lastname: Chaudhuri
authors.forename: Lauren
authors.initials: L
authors.lastname: Nathan
authors.forename: Lesley
authors.initials: L
authors.lastname: Tinker
authors.forename: Simin
authors.initials: S
authors.lastname: Liu
mesh_terms: D002097:C-Reactive Protein / Q000235:genetics*; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D018570:Risk Assessment; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein