Common Variations in the Genes Encoding C-Reactive Protein, Tumor Necrosis Factor-α, and Interleukin-6, and the Risk of Clinical Diabetes in the Women's Health Initiative Observational Study

被引：17

作者：

Chan, Kei-hang K. ^{[1
,2
]}

Brennan, Kathleen ^{[1
,3
]}

You, Nai-chieh Y. ^{[1
,2
]}

Lu, Xuyang ^{[2
,4
]}

Song, Yiqing ^{[5
,6
]}

Hsu, Yi-Hsiang ^{[7
,8
]}

Chaudhuri, Gautum ^{[1
,3
]}

Nathan, Lauren ^{[1
,3
]}

Tinker, Lesley ^{[9
]}

Liu, Simin ^{[1
,2
,10
,11
]}

机构：

[1] Univ Calif Los Angeles, Ctr Metab Dis Prevent, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Epidemiol, Program Genom & Nutr, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA

[5] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Boston, MA USA

[7] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA

[8] Harvard Univ, Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA

[9] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[10] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

[11] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

来源：

CLINICAL CHEMISTRY | 2011年 / 57卷 / 02期

关键词：

PROMOTER POLYMORPHISM; MULTIETHNIC COHORT; INSULIN-RESISTANCE; METABOLIC SYNDROME; LARGE-SCALE; IL6; GENE; MELLITUS; VARIANTS; ASSOCIATION; AND-308;

D O I：

10.1373/clinchem.2010.154526

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

BACKGROUND: Circulating concentrations of high-sensitivity C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), 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- alpha, 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-alpha receptor 2 (TNF-alpha-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-alpha-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-alpha-R2. Common variants of the CRP, TNF, and IL6 genes were not significantly associated with risk of clinical diabetes in postmenopausal women. (C) 2010 American Association for Clinical Chemistry

引用

页码：317 / 325

页数：9

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