Association of the tumour necrosis factor α -308G/A polymorphism with the risk of diabetes in an elderly population-based cohort

被引:50
作者
Heijmans, BT
Westendorp, RGJ
Droog, S
Kluft, C
Knook, D
Slagboom, PE
机构
[1] Leiden Univ, Med Ctr, Dept Gen Internal Med, Gerontol & Geriatr Sect, NL-2300 RA Leiden, Netherlands
[2] TNO Prevent & Hlth, Gaubius Lab, Leiden, Netherlands
关键词
tumour necrosis factor alpha; polymorphism; linkage disequilibrium; diabetes mellitus; cardiovascular disease; mortality;
D O I
10.1038/sj.gene.6363859
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Ample evidence supports a role for tumour necrosis factor alpha (TNFalpha) in the development of type 2 diabetes and cardiovascular disease. TNFalpha expression was found to be influenced by a -308G/A polymorphism in the promoter of the gene encoding TNFalpha (TNF). We investigated the contribution of this polymorphism to diabetes and cardiovascular mortality in a population-based cohort of 664 subjects aged 85 years and over (Leiden 85-plus Study). The -308G/A TNF promoter polymorphism was associated with the prevalence of diabetes in old age (P = 0.006). The risk of diabetes among subjects homozygous for the A-allele was estimated to be 4.6-fold (95% Cl, 1.6-13.3) higher than among subjects homozygous for the common G-allele. The promoter polymorphism did not, however, predict mortality from all causes, cardiovascular diseases, cancer or infectious diseases during a 10-year follow-up period. In addition to the promoter polymorphism, TNFa and TNFc microsatellite genotypes were determined but these polymorphisms were not associated with morbidity or mortality. In conclusion, the -308G/A polymorphism in the TNF promoter is strongly associated with the risk of diabetes but not cardiovascular mortality in old age.
引用
收藏
页码:225 / 228
页数:4
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