Decreased frequency of the TNF2 allele of TNF-α −308 promoter polymorphism is associated with lacunar infarction

Abstract

Background and purpose Enhanced release of proinflammatory cytokines may contribute to the pathogenesis of stroke. It was examined whether G to A promoter polymorphism in the tumor necrosis factor-α gene at position −308 affects the risk of stroke. Methods We genotyped 336 patients with ischemic stroke and 333 healthy controls for this polymorphism. Patients were divided into different groups based on the Oxfordshire Community Stroke Project (OCSP) or a modified TOAST classification. Distribution of the alleles at −308 G > A promoter polymorphism was determined by PCR–RLFP method. Results Patients with ischemic stroke had a significantly ( p < 0.001) decreased (0.115) frequency of the −308 A (TNF2) allele compared to the healthy controls (0.196). When patients were categorized according to the OCSP classification, it turned out that significant ( p = 0.002) decrease in TNF2 allele frequency (0.065) was restricted to the patients with lacunar infarct (LACI) whereas the frequency of the TNF2 alleles in patients with the other three subtypes (TACI, PACI, and POCI) did not significantly differ from that in healthy controls. Similar results were obtained when the patients were divided according to the modified TOAST classification: the frequencies of the TNF2 allele were 0.068 and 0.140 ( p = 0.010) in the patients with small-vessel and non-small vessel (large vessel infarction or ischemic stroke of other origin) infarction, respectively. The age-adjusted odds ratio of the patients carrying the TNF2 allele to develop lacunar infarct was 0.33 (0.16–0.68) ( p = 0.002) compared to the non-carriers. This difference was also restricted to the male patients. Conclusions Our results suggest that male carriers of TNF2 allele are less susceptible for the development of lacunar subtype of ischemic stroke than the non-carriers.