Association of TNF-α gene polymorphisms with systemic lupus erythematosus in Taiwanese patients

Tumour necrosis factor-α (TNF-α), an important proinflammatory cytokine, exerts a variety of physiological and pathogenic effects that lead to tissue destruction. Studies on the association of TNF-α genetic polymorphisms with systemic lupus erythematosus (SLE) have yielded inconclusive results. We investigated the association of TNF-α genetic polymorphisms (−1031T/C, −863C/A, −857T/C, −308A/G and +489A/G) with SLE in Taiwanese patients and controls. Our results indicate that 1) the frequency of the A-allele at −863 position was significantly higher in SLE patients (odds ratio = 1.46; 95% CI = 1.02–2.08); 2) the frequency of the A-allele at +489 position was significantly higher in SLE patients (odds ratio = 1.79; 95% CI = 1.21–2.65); 3) the AA or GA genotype frequencies at +489 position were significantly increased in SLE patients (AA genotype: odds ratio = 11.20; 95% CI = 1.36–92.55; GA genotype: odds ratio = 1.63; 95% CI = 1.03–2.58); 4) no significant association of TNF-α haplotypic distributions was observed, except for the haplotypes TCCGA, CACGA and CCCGG; and 5) the genotype frequency of the polymorphisms at −1031 was significantly different in patients with antinuclear antibodies ( P = 0.022). The allele and genotype frequencies of the polymorphisms at −863 were not significantly different. The genotype frequency of the polymorphisms at −857 was significantly different in patients with haematological disorder ( P = 0.025). The frequency of A allele of the polymorphisms at −308 was significantly increased in patients with malar rash ( P = 0.033), discoid rash ( P = 0.023), photosensitivity ( P = 0.037), oral ulcers ( P = 0.002) and serositis ( P = 0.029). The genotype frequency of the polymorphisms at +489 was significantly different in patients with discoid rash and photosensitivity (data not shown; discoid rash, P = 0.031; photosensitivity, P = 0.044). These results suggest that TNF-α genetic polymorphisms contribute to SLE susceptibility in the Taiwanese population.