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目的 探究PROS1基因单核苷酸多态性(SNP)与包头地区汉族人群复发性流产(RSA)发生风险之间的相关性。方法 选取RSA患者及对照人群各158例作为研究对象，测定蛋白S、蛋白C、抗凝血酶-Ⅲ活性；使用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术对PROS1基因rs13062355、rs6441600和rs12634349位点进行基因分型。采用非条件性Logistic回归分析PROS1基因三种SNP与RSA发生风险的相关性。结果 RSA患者的蛋白S、抗凝血酶-Ⅲ活性下降(P<0.05);PROS1 SNP rs13062355在显性模型下与RSA发病风险相关：与携带TT基因型患者比较，携带CT+CC基因型的患者RSA发病风险下降(OR=0.398,95%CI:0.249～0.638)。SNP rs6441600、rs12634349与RSA的发病风险无关联。在PROS1 rs13062355、rs6441600、rs12634349构建的单体型中，单体型C-C-C在两组间差异有统计学意义(P<0.05);三阶交互模型rs13062355-rs6441600-rs12634349与RSA发病风险相关。结论 PROS1 SNP rs13062355可能与包头地区汉族女性RSA患病风险相关；PROS1 rs13062355、rs6441600、rs12634349的单体型C-C-C降低了RSA发病风险；三阶模型rs13062355-rs6441600-rs12634349的交互作用在RSA的发生中具有协同效应。
Abstract：Objective To investigate the association between single nucleotide polymorphism(SNP) of PROS1 gene and recurrent spontaneous abortion(RSA) in Baotou Han population. Methods 158 RSA patients and 158 control subjects were selected as the study subjects, and the activities of protein S, protein C and antithrombin-Ⅲ were measured. The rs13062355, rs6441600 and rs12634349 loci of PROS1 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Non-conditional Logistic regression was used to analyze the correlation between three SNPs of PROS1 gene and the risk of RSA. Results The protein S and antithrombin-Ⅲ activities of RSA patients decreased significantly(P<0.05). PROS1 SNP rs13062355 was associated with the risk of RSA under the dominant model: compared with genotype TT, patients with CT+CC genotypes had a reduced risk of RSA(OR=0.398, 95%CI: 0.249-0.638); SNP rs6441600 and rs12634349 were not associated with the risk of RSA(P>0.05). In the haplotypes constructed by PROS1 rs13062355, rs6441600 and rs12634349, Haplotype C-C-C was statistically different between the two groups(P<0.05). The third-order interaction model rs13062355-rs6441600-rs12634349 was associated with the risk of RSA. Conclusion PROS1 SNP rs13062355 may be associated with the risk of RSA in Han women in Baotou area. Haplotype C-C-C of PROS1 rs13062355, rs6441600 and rs12634349 reduces the risk of RSA. The third-order model rs13062355-rs6441600-rs12634349 interaction has a synergistic effect on the occurrence of RSA.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2025.02.008
中图分类号:R714.21
引用信息:
[1]赵萍萍,吴涤,李得春,等.PROS1基因多态性与包头地区汉族人群复发性流产的关联性[J].安徽医科大学学报,2025,60(02):240-246.DOI:10.19405/j.cnki.issn1000-1492.2025.02.008.
基金信息:
内蒙古自治区卫生健康科技计划项目(编号：202201429); 包头医学院青年科技人才发展计划(编号：BYJJ-QNGG 2022044)~~