Khadzhieva M B, Lutcenko N N, Volodin I V, Morozova K V, Salnikova L E
N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences , Moscow , Russia.
Free Radic Res. 2014 May;48(5):534-41. doi: 10.3109/10715762.2014.891735. Epub 2014 Mar 5.
Oxidative stress may play a role in the recurrent miscarriage (RM) with no known etiology. This study was conducted to investigate the association of polymorphisms in oxidative stress-related genes with idiopathic RM. A total of 331 idiopathic RM patients and 197 controls were genotyped for ABCB1 rs1045642, CYP1A1 rs1048943 and rs4646903, COMT rs4680, CAT rs17880664, GCLC rs17883901, GPX4 rs713041, NRF2 rs6721961, SOD2 rs4880, and OGG1 rs1052133. A protective effect of COMT rs4680-G allele on RM was shown in individual SNP analysis: P = 0.0016, OR = 0.47, 95% CI 0.29-0.75. The multi-factor dimensionality reduction (MDR) approach revealed gene-gene interactions for ABCB1, COMT, GPX4, and OGG1 genes. Cumulative gene risk score analysis demonstrated that more than three risk alleles in the genes ABCB1 (rs1045642-T), COMT (rs4680-A), GPX4 (rs713041-T), and OGG1 (rs1052133-G) were associated with idiopathic RM P = 1.2 × 10(-3), OR = 1.97, 95% CI 1.31-2.97. In silico data interpreting by GeneMANIA analysis revealed genetic, physical, pathway, and coexpression networks for these four genes.
氧化应激可能在病因不明的复发性流产（RM）中起作用。本研究旨在调查氧化应激相关基因多态性与特发性RM的关联。对331例特发性RM患者和197例对照进行了ABCB1 rs1045642、CYP1A1 rs1048943和rs4646903、COMT rs4680、CAT rs17880664、GCLC rs17883901、GPX4 rs713041、NRF2 rs6721961、SOD2 rs4880和OGG1 rs1052133的基因分型。单核苷酸多态性分析显示COMT rs4680 - G等位基因对RM有保护作用：P = 0.0016，OR = 0.47，95% CI 0.29 - 0.75。多因素降维（MDR）方法揭示了ABCB1、COMT、GPX4和OGG1基因之间的基因 - 基因相互作用。累积基因风险评分分析表明，ABCB1（rs1045642 - T）、COMT（rs4680 - A）、GPX4（rs713041 - T）和OGG1（rs1052133 - G）基因中超过三个风险等位基因与特发性RM相关，P = 1.2×10⁻³，OR = 1.97，95% CI 1.31 - 2.97。通过GeneMANIA分析进行的计算机数据解释揭示了这四个基因的遗传、物理、通路和共表达网络。
