Association of the tumour necrosis factor alpha -308G/A polymorphism with the risk of diabetes in an elderly population-based cohort.
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% CI, 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.
Heijmans
B T
BT
Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands. b.t.heijmans@lumc.nl
Westendorp
R G J
RG
Droog
S
S
Kluft
C
C
Knook
D L
DL
Slagboom
P E
PE
D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D009026:Mortality; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha