维生素D受体ApaI多态性与系统性红斑狼疮的相关性研究

Association of vitamin D receptor gene Apa I polymorphism with systemic lupus erythematosus

目的检测维生素D受体（vDrt）基因ApaI多态性在系统性红斑狼疮（SLE）患者中的分布，并探讨其与SLE发病的相关性。方法应用聚合酶链反应一限制性片段长度多态性（PCR—RFLP）技术，检测VDR基因ApaI多态性等位基因及基因型在244例SLE患者和162名健康对照者中的分布情况，经r检验和方差分析分析其与SLE发病的关系及对SLE患者临床的影响。结果VDRApaI多态性等位基因A和a的分布频率在健康对照组和SLE组差异无统计学意义（P=0．860），但Aa基因型分布频率在SLE组中为38．9％，显著高于健康对照组的22．2％（r=12．442，P=0．000），Aa基因型个体发生SLE的相对危险度[比数比（0R）=2．232，95％CI=1．421～3．503，x^2=12．442，P=0．000]，而AA和aa基因型分布频率在健康对照组和SLE组则无明显差异（P=0.098和P=0．067）。进一步分析VDRApaI多态性基因型与SLE病情的关系发现，杂合子Aa基因型患者中浆膜炎发生率更高（P=O．000），而纯合子AA基因型患者则更易出现肾脏损害（P=0．016），伴随较高阳性率的抗dsDNA抗体（P=0．014）。结论VDRApaI多态性Aa杂合子基因型与SLE发病易感性有关，并且患者更易发生浆膜炎；而纯合子AA基因型对患者出现。肾脏损害和抗dsDNA抗体的生成有明显影响。

Objective To determine the distribution of vitamin D receptor （VDR） gene Apa Ⅰ polymorphism and the possible association with systemic lupus erythematosus （SLE） in Chinese Han population. Methods Genomic DNA from 244 Chinese SLE patients and 162 sex and ethnically matched controls were typed for VDR Apa I polymorphism by polymerase chain reaction restriction fragment length polymorphism （PCR-RFLP）. Frequency distribution was compared between patients and the controls using Chi-Square test. Clinical characteristics were analyzed between different Apa Ⅰ genotypes and between alleles using Chi-Square test and analysis of variance. Results There was no significant difference in the distribution frequencies of Apa Ⅰ alleles between SLE patients and the controls, but the distribution frequency of heterozygote Aa in SLE patients was higher than that in the controls （38.9% vs 22.2%, X2=12.442, P=0.000）. The relative risk for heterozygote Aa was 2.232（95%CI=1.421-3.503, X2=12.442, P=0.000）. No significant difference was observed between SLE patients and the controls with regard to homozygote AA or homozygote aa （P=0.098, P=0.067, respectively）. Furthermore, when analyzing the effects of VDR Apa Ⅰ polymorphism on the symptoms of SLE, significant difference was observed, with SLE patients carrying heterozygote Aa developed serositis （P= 0.000）, and those carrying homozygote AA developed renal disorder （P=-0.01） along with the presence of anti-dsDNA antibody （P=0.014）. Conclusion There is a significant association between VDR gene heterozygote Aa and the incidence of systemic lupus erythematosus in Han population of China, the heterozygote Aa is also involved in serositis. Although there is no association between homozygote AA and the incidence of systemic lupus erythematosus, homozygote AA is involved in renal disorder and has a positive effect on anti-dsDNA antibody production.