TNF-α gene polymorphisms: association with age-related macular degeneration in Russian population

AIM: To study polymorphisms in promotor regions of tumor necrosis factor(TNF)-α TNF-863 A/C(rs1800630), TNF-308 A/G(rs1800629), and TNF-238 A/G(rs361525) in patients with age-related macular degeneration(AMD) and associations of complex TNF-α genotypes with AMD. METHODS: One hundred and two patients(82 women, 20 men; mean age 64.2±1.2 y) with AMD and 100 healthy age-and sex-matched controls(82 women, 18 men; 60±1.4 y) were included in the study. All subjects were Caucasian, all subjects and their parents were inhabitants of Russia. Genomic DNA was obtained from EDTA-preserved blood using the standard phenol-chloroform method. Polymorphisms were detected by polymerase chain reaction followed by the restriction fragment length polymorphism method. The following TNF-α genotypes were studied: TNF-α-238 AA, GA, GG, TNF-α-308 AA, GA, GG, TNF-α-863 AA, CA, CC. RESULTS: Differences in TNF-α-863 and TNF-α-238 genotypes frequencies in patients with AMD and healthy controls were not found. The distribution of TNF-α-308 AA and TNF-α-308 GA genotypes was significantly different between the studied group and the controls [odds ratios(OR) =0.22, P=0.0287 and OR=2.91, P=0.0063, respectively]. TNF-863 CC/TNF-308 GA and TNF-308 GA/TNF-238 GG genotypes were associated with the increased risk of AMD(OR=2.48, P=0.0332 and OR=2.51, P=0.0187, respectively). Five genotypes combinations appeared to be protective. CONCLUSION: In the present study, single nucleotide polymorphisms and complex polymorphisms of one of the key inflammatory cytokines TNF-α, and a number of significant associations of these polymorphisms with AMD in Russian population have been shown. Complexanalysis of genotypes could be important in AMD risk factors detection and studying pathogenesis.