Association of the TNFa13 microsatellite with systemic sclerosis in Japanese patients

Objectives-To elucidate the contribution of microsatellite polymorphisms of TNFa and TNFb alleles to the pathogenesis of systemic sclerosis (SSc) by c omparing the allele distribution among populations with different HLA susce ptibility genes in SSc. Methods-TNFa and TNFb microsatellite polymorphisms were determined by PCR i n 54 Japanese and 50 German SSc patients and in normal controls. HLA-DR gen otyping was carried out by PCR-SSCP. Results-The frequency of TNFa13 was significantly increased in Japanese SSc (p=0.011, OR=8.53, 95% confidence intervals (95%CI)=2.46, 32.51, and p<1.0 x 10E-5, OR=10.35, 95%CI=4.88, 22.09) and SSc with antitopoisomerase I ant ibody (a-Scl-70) (p=0.021, OR=33.25, 95%CI=3.39, 800.76, and p<1.0 x 10E-5, OR=24.42, 95%CI=8.40, 72.83), compared with the German patient group and G erman controls, respectively. This increase was not only attributable to a higher prevalence of TNFa13 in Japanese compared with Germans (p=0.005, OR= 3.55, 95%CI=1.60, 7.85) but was also caused by an increase in SSc, especial ly in the a-Scl-70 positive patients (p=0.028, OR=6.88, 95%CI=1.16, 22.60) compared with Japanese controls. TNFa13 was positively in linkage disequili brium with HLA-DRB1*1502 (LD=0.053, t=2.69). Association analysis indicated that both TNFa13 and DRB1*1502 might have comparable probabilities of bein g susceptibility factors for SSc with a-Scl-70 in Japanese. Prevalences of TNFa6 and 13 were significantly increased and prevalences of TNFa2, and 7 w ere significantly decreased in Japanese controls as compared with German co ntrols. Conclusion-TNFa13 is a genetic marker for SSc with a-Scl-70 in Japanese pat ients. Various differences in the prevalences of TNFa alleles between Japan ese and German controls were established.