Takeuchi F, Nabeta H, Füssel M, Conrad K, Frank K H
Department of Internal Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8855, Japan.
Ann Rheum Dis. 2000 Apr;59(4):293-6. doi: 10.1136/ard.59.4.293.
To elucidate the contribution of microsatellite polymorphisms of TNFa and TNFb alleles to the pathogenesis of systemic sclerosis (SSc) by comparing the allele distribution among populations with different HLA susceptibility genes in SSc.
TNFa and TNFb microsatellite polymorphisms were determined by PCR in 54 Japanese and 50 German SSc patients and in normal controls. HLA-DR genotyping was carried out by PCR-SSCP.
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 antibody (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 German 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, especially 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 disequilibrium with HLA-DRB11502 (LD=0.053, t=2.69). Association analysis indicated that both TNFa13 and DRB11502 might have comparable probabilities of being susceptibility factors for SSc with a-Scl-70 in Japanese. Prevalences of TNFa6 and 13 were significantly increased and prevalences of TNFa2, and 7 were significantly decreased in Japanese controls as compared with German controls.
TNFa13 is a genetic marker for SSc with a-Scl-70 in Japanese patients. Various differences in the prevalences of TNFa alleles between Japanese and German controls were established.
通过比较系统性硬化症（SSc）中具有不同HLA易感基因的人群的等位基因分布，阐明TNFα和TNFβ等位基因的微卫星多态性对SSc发病机制的贡献。
采用聚合酶链反应（PCR）检测54例日本和50例德国SSc患者及正常对照者的TNFα和TNFβ微卫星多态性。通过PCR-SSCP进行HLA-DR基因分型。
与德国患者组和德国对照组相比，日本SSc患者（p = 0.011，比值比（OR）= 8.53，95%置信区间（95%CI）= 2.46，32.51，且p < 1.0×10⁻⁵，OR = 10.35，95%CI = 4.88，22.09）及抗拓扑异构酶I抗体（抗Scl-70）阳性的SSc患者（p = 0.021，OR = 33.25，95%CI = 3.39，800.76，且p < 1.0×10⁻⁵，OR = 24.42，95%CI = 8.40，72.83）中TNFα13的频率显著增加。这种增加不仅归因于与德国人相比日本人中TNFα13的患病率更高（p = 0.005，OR = 3.55，95%CI = 1.60，7.85），还由于与日本对照组相比，SSc患者尤其是抗Scl-70阳性患者中TNFα13的频率增加（p = 0.028，OR = 6.88，95%CI = 1.16，22.60）。TNFα13与HLA-DRB11502呈正连锁不平衡（连锁不平衡系数（LD）= 0.053，t = 2.69）。关联分析表明，在日本人群中，TNFα13和DRB11502作为抗Scl-70阳性SSc易感性因素的可能性相当。与德国对照组相比，日本对照组中TNFα6和13的患病率显著增加，而TNFα2和7的患病率显著降低。
TNFα13是日本患者抗Scl-70阳性SSc的遗传标志物。确定了日本和德国对照组之间TNFα等位基因患病率的各种差异。
