温州汉族SLE患者载脂蛋白H基因Leu247Val多态性与抗磷脂抗体的相关性研究

目的 探讨apoH第7号外显子G817T（Leu247Val）的多态性与温州地区汉族SLE患者抗磷脂抗体产生的关系。方法 收集温州地区汉族SLE患者165例及健康体检者160例，PCR技术及DNA测序技术检测apoH第7号外显子G817T（Leu247Val）的多态性；蝰蛇毒试验法测定狼疮抗凝物（LAC）比值，ELISA法测定其抗β2糖蛋白I（β2GPI）抗体及抗心磷脂抗体（ACA）。用Logistic回归分析Leu247Val多态性与抗磷脂抗体（APL）的关系。结果 SLE患者组与健康对照组G817T位点的基因型构成及等位基因频率差异有统计学意义（P值均 < 0.01），患者组TT、GT基因型及T等位基因频率较高，而GG基因型及G等位基因频率偏低。G817T位点的基因型分布与LAC，抗β2GPI抗体及ACA的阳性均有关（P值 < 0.05，< 0.01，< 0.05）。GT基因型是LAC（P < 0.05，OR = 2.33，95% CI 1.18 ~ 4.59）、抗β2GPI抗体（P < 0.01，OR = 5.92， 95% CI 2.61 ~ 13.46）及ACA（P < 0.05，OR = 2.52，95% CI 1.22 ~ 5.24）产生的危险因素。TT基因型是抗β2GPI抗体的危险因素（P < 0.01，OR = 5.84，95% CI 1.69 ~ 20.20）。结论 温州地区汉族SLE患者apoH第7号外显子G817T（Leu247Val）位点的多态性与APL产生有关，GT、TT基因型是APL产生的危险因素。

Relationship between the valine/leucine247 polymorphism of apolipoprotein H gene and generation of antiphospholipid antibodies in patients of Han nationality with systemic lupus erythematosus in Wenzhou region

ZHU Li-qing*, XIE Hai-xiao, YANG Li-hong, JIN Yan-hui, HU Wang-qiang, WANG Ming-shan, SHI Hong-ying, XU Peng-fei, ZHU Xiao-chun. *Laboratory Diagnostic Center, First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, Zhejiang, China Corresponding author: WANG Ming-shan, Email：wywms@126.com 【Abstract】 Objective To study the relationship between the valine/leucine247 （817G/T） polymorphism in exon 7 of apolipoprotein H （apoH） gene and the generation of antiphospholipid（APL）antibodies in patients of Han nationality with systemic lupus erythematosus （SLE） in Wenzhou region. Methods This study included 165 patients with SLE and 160 healthy controls of Han nationality in Wenzhou region. Venous blood samples were obtained from all of the subjects followed by the isolation of blood plasma, sera and white blood cells. PCR and DNA sequencing were carried out to assess the Leu/Val247 polymorphism in apoH gene. Lupus anticoagulant （LAC） was detected by Russell viper venom time （RVVT） assay. Enzyme-linked immunosorbent assay （ELISA）was carried out to quantify the serum levels of anti-β2-glycoprotein I （GPI） antibodies and anticardiolipin antibodies（ACA）. Chi-square test was carried out to compare the 817G/T polymorphism between the patients and controls, and Logistic regression analysis to evaluate the correlation between the 817G/T polymorphism and production of antiphospholipid antibodies. Results There were significant differences between the patients and controls in the genotype distribution and allele frequency at position 817 of apoH gene （both P < 0.01）. The TT, GT genotypes and T allele were more frequent, while GG genotype and G allele were less frequent, in the patients than in the controls. The GT genotype at position 817 was a risk factor for the production of LAC（P < 0.05, OR = 2.33, 95%CI = 1.18 － 4.59）, anti-β2GPI antibodies（P < 0.01, OR = 5.92, 95%CI = 2.61 － 13.46） and ACA（P < 0.05, OR = 2.52, 95%CI = 1.22 － 5.24）, and the TT genotype was associated with an increased frequency of anti-β2GPI antibodies （P < 0.01, OR = 5.84, 95%CI = 1.69 － 20.20）. Conclusions The 817G/T（Leu/Val247） polymorphism in exon 7 of apoH gene is associated with the generation of APL antibodies in patients of Han nationality with SLE in Wenzhou region. The TT and GT genotypes at position 817 of apoH gene appear to be a risk factor for the production of APL antibodies. 【Key words】 Lupus erythematosus, systemic; beta 2-glycoprotein I; Genes; Lupus coagulation inhibitor