IFNG基因与陕西子痫前期人群遗传易感性的相关性研究

Association of IFNG gene polymorphisms with susceptibility to preeclampsia among pregnant woman from Shaanxi

目的探讨IFNG基因单核苷酸多态性（single nucleotide polymorphism，SNPs）与陕西人群子痫前期（preeclampsia，PE）之间的相关性。方法应用SNaPshot方法测定280例PE患者和344名正常孕妇IFNG基因5个SNPs（rs2069705、rs2430561、rsl861493、rs2069718、rs2193050）位点的基因型；酶联免疫ELISA法检测血浆干扰素γ（Interferon-γ，IFN-γ）浓度；统计分析采用SPSS17软件，基因分型数据经体重指数和年龄Logistic回归方法校正。连锁不平衡分析采用Hapview4．2软件。结果所选IFNG基因5个SNP位点均符合Hardy-Weinberg平衡检验（P〉0．05）。IFNG基因内含子区域rs2430561T等位基因频率（OR=1．54，95％CI：1．15～2．09，P=6．99×10-3），显性模式（OR=3．77，95％CI：1．09～13．29，P=0．029）、隐性模式（OR=1．53，95％CI：1．09～2．15，P=0．018）在PE组与对照组比较差异有统计学意义。PE组rs2430561位点TT基因型IFN-γ浓度[（13．69±0．79）pg／mL]高于AA基因型和AT基因型[（13．11±1．56）pg／mL]，两者IFN-γ血浆浓度比较差异有统计学意义（P〈O．05）。rs2069705、rsl861493、rs2069718和rs2193050位点等位基因、显性模式和隐性模式三者在PE组与对照组比较差异均无统计学意义（P〉O．05）。结论IFNG基因内含子区域rs2430561单核苷酸多态性位点，可能是陕西汉族子痫前期人群的易感基因位点；纯合子TT基因型IFN-γ浓度高于纯合子AA基因型和杂合子AT基因型。

Objective To assess the association of IFNG gene polymorphisms with preeclampsia among pregnant woman from Shaanxi Province. Methods Genomic DNA was extracted from peripheral blood samples collected from 280 patients with preeclampsia and 344 healthy pregnant women. Five tag single nucleotide polymorphisms （SNPs） of the IFNG gene （ rs2069705, rs2430561, rs1861493, rs2069718, and rs2193050） were genotyped with a SNaPshot method. Genotypic and allelic frequencies were evaluated with a Chi square test. Genotype data was corrected by Logistic regression for body mass index and age. The level of IFN-γ was determined with an ELISA assay. Results The distribution of five tag SNPs all conformed to Hardy-Weinberg equilibrium （P：〉0.05）. Significant association with preeclampsia was found with the T allele of rs2430561 （OR=1. 54, 95% CI：1. 15-2.09, P=6. 99X10-3）, under a dominant model （0R=3.77, 95% CI：1.09-13.29, P=0. 029） and a recessive model （OR=I. 53, 95% I： 1.09-2.15, P=0. 018）. For the patient group, the IFN-γ level of those with a TT genotype for rs2430561 was significantly higher than those with an AA or AT genotype [（13.69±0.79） pg/mL vs. （13.11±1.56） pg/mL, P〈0. 051. Conclusion Polymorphism of the rs2430561 locus of the IFNG gene is associated with increased risk for preeclampsia as well as serum level of IFN γ among pregnant woman from Shaanxi. The role of the IFNG gene in the regulation of preeclampsia requires further investigation.