系统性红斑狼疮患者132糖蛋白Ⅰ基因G817T（Val247Leu）和G1025C（Trp316Ser）多态性与抗磷脂抗体及血栓并发症的相关性研究  

Va1247Leu and Trp316Ser poly morphisms of β2-glycoprotein I in systemic lupus erythematosus patients and their associations with antiphospholipid antibodies and thrombotic complications

作　　者：赵秘胜 王晗 夏雯丽 朱小春[2] 朱丽青[3] 

机构地区：[1]浙江省温州市人民医院检验科,325000 [2]温州医科大学附属第一医院风湿免疫科 [3]温州医科大学附属第一医院检验科

出　　处：《中华风湿病学杂志》2016年第5期292-298,共7页Chinese Journal of Rheumatology

基　　金：国家自然科学基金青年基金（81501810）;浙江省自然科学基金（LQ15H200001）

摘　　要：目的探讨SLE患者β2糖蛋白I（β2GPI）基因G817T（Val247Leu）和G1025C（Trp316Ser）多态性与抗磷脂抗体（APLs）、血栓及妊娠并发症的相关性。方法分析378例SLE患者的临床资料，收集其血液标本，DNA测序分析Val247Leu和Trp316Ser多态性；ELISA法检测抗β2GPI抗体和抗心磷脂抗体（ACA）；蝰蛇毒凝固法测定狼疮抗凝物（LAC）。将SLE患者按照APLs（抗β2GPI抗体、LAC、ACA）、血栓及妊娠并发症进行分组，用Logistic回归法分析上述因素与Val 247Leu和Trp316Ser多态性的相关性。结果健康对照组Val247Leu位点的主要基因型是LL，占57．08％，而SLE患者组为VL，占59．5％0（2=45．01，P=0．000）。Val247Leu的基因型构成与APLs、血栓及妊娠并发症的发生均有关。VV基因型是并发血栓的高危因素（OR=6．79，P=0．000），也是产生抗β2GPI抗体（OR=3．75，P=0．000）、ACA（OR=2．12，P=-0．044）及妊娠并发症（OR=3．85，P=-0．017）发生的危险因素。vL基因型是抗B，GPI抗体（OR=2．95，P=0．000）、LAC（OR=I．88，P=0．007）、ACA（OR=2．47，P=0．000）产生的危险因素，也是并发血栓（OR=2．97，p=0．001）及妊娠并发症（OR=2．74，P=0．016）的危险因素。Try316Ser位点以TT基因型为主，其次为TS，基因型构成在SLE患者与对照组间无差异，与APk、血栓及妊娠并发症均无相关性。结论SLE患者Val 247Leu多态性与APLs的产生、血栓形成及妊娠并发症的发生均有关。VV、VL基因型是产生APLs，发生血栓及妊娠并发症的危险因子。尤其是vv基因型，是血栓形成的高危因素。TW316Ser多态性与APh的产生、血栓及妊娠并发症的发生均无关。Objective To study the Va1247Leu and Trp316Ser polymorphisms of β2-glycoprotein I （β2GP I ） in systemic lupus erythematosus （SLE） patients and their associations with antiphospholipid antibodies and thrombotic complications. Methods We used DNA sequencing to detect the polymorphisms of Va1247Leu and Trp316Ser in 378 SLE patients and 240 normal controls. Anti-β2GP I antibodies and anticardiolipin （ACA） were tested by enzyme linked immunosorbent assay （ELISA）. Lupus-type anticoagulants （LAC） was performed by diluted Russell＇s Viper Venom Test. Then the patient group was further analyzed according to APLs （Anti-β2GP I antibody, LAC and ACA）, thrombosis and obstetrical complications using Logistic regression analysis to confirm whether there are associations between β2GP 1 polymorphism and those factors. Results For Va1247Leu, the predominant genotype was LL in healthy controls which accounted for 57.08%, while it was VL in SLE patients which accounted for 59.5% （X2=45.01, P=0.000）. Frequency of VV genotype was significantly higher in patients with thrombosis, antiβ2GP I, ACA and obstetrical complications （0R=6.79, 3.75, 2.12 and 3.85, respectively; P=0.000, 0.001, 0.044 and 0.017, respectively）. Those patients with VL genotype tended to have positive anti-β2GPI, LAC, ACA, thrombosis and also obstetrical complications （OR=2.95, 1.88, 2.47, 2.97 and 2,74, respectively; P=0.000, 0.007, 0.000, 0.001 and 0.016, respectively） than those negative ones. The predominant genotype of Trp316Ser was TT, then TS. No correlations could be found between Trp316Ser polymorphism and APLs, neither relation to thrombosis complications. Conclusion The polymorphism of Va1247Leu is significantly associated with the presence of APLs, thrombosis and obstetrical complications. Both VV and VL genotype are risk factors for the generation of APLs, occurrence of thrombosis and obstetrical complications. The VV genotype is a high risk factor for thrombosis. Trp316Ser polymorphism does not contribute to

关 键 词：红斑狼疮 系统性 Β2糖蛋白I 抗体 抗磷脂 

分 类 号：R593.241[医药卫生—内科学] R446.6[医药卫生—临床医学]