Li Li, Liu Jia, Qin Shuang, Li Ruiman
Department of Obstetrics and Gynecology, First Affiliate Hospital of Jinan University.
Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou, China.
Medicine (Baltimore). 2018 Oct;97(40):e12561. doi: 10.1097/MD.0000000000012561.
This study aimed to reveal the genetic association between polymorphisms in promoter region of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) and the risk of recurrent spontaneous abortion (RSA) in Chinese population.A total of 129 RSA patients and 116 relative controls were selected and the genotyping of polymorphism was conducted by polymerase chain reaction with sequencing. Genotype distribution of polymorphism in the control group was tested the status of Hardy-Weinberg equilibrium and then, genotype frequencies were compared between the case and control groups by chi-squared test. Odds ratio (OR) with the corresponding 95% confidence interval (95% CI) was computed to express the risk of RSA caused by polymorphism. Moreover, the linkage disequilibrium of polymorphisms in MMP2 was analyzed by Haploview software.CT genotype and T allele of rs243865 in MMP2 were significantly associated with the increased susceptibility to RSA in Chinese population (CT vs. CC: OR = 1.926, 95% CI = 1.101-3.368; T vs. C: OR = 1.751, 95% CI = 1.146-2.676). Similarly, CT genotype carriers of rs3918242 in MMP9 were obviously more in RSA patients than that of the controls (P = .037), which indicated it was associated with the risk of RSA occurrence (OR = 1.760, 95% CI = 1.034-2.995). So was T allele in RSA development (OR = 1.595, 95% CI = 1.061-2.398). Haplotypes C-T and T-C were also the risk factors of RSA (OR = 1.673, 95% CI = 1.103-2.536; OR = 2.171, 95% CI = 1.372-2.436).MMP2 rs243865 and MMP9 rs3918242 polymorphisms are significantly associated with the risk of RSA in Chinese population.
本研究旨在揭示中国人群中基质金属蛋白酶2（MMP2）和基质金属蛋白酶9（MMP9）启动子区域多态性与复发性自然流产（RSA）风险之间的遗传关联。共选取129例RSA患者和116例相关对照，采用聚合酶链反应测序法进行多态性基因分型。检测对照组多态性的基因型分布是否符合哈迪-温伯格平衡状态，然后通过卡方检验比较病例组和对照组之间的基因型频率。计算比值比（OR）及相应的95%置信区间（95%CI）以表达多态性导致RSA的风险。此外，使用Haploview软件分析MMP2多态性的连锁不平衡。MMP2中rs243865的CT基因型和T等位基因与中国人群中RSA易感性增加显著相关（CT与CC：OR = 1.926，95%CI = 1.101 - 3.368；T与C：OR = 1.751，95%CI = 1.146 - 2.676）。同样，MMP9中rs3918242的CT基因型携带者在RSA患者中明显多于对照组（P = 0.037），这表明其与RSA发生风险相关（OR = 1.760，95%CI = 1.034 - 2.995）。RSA发生过程中T等位基因也是如此（OR = 1.595，95%CI = 1.061 - 2.398）。单倍型C - T和T - C也是RSA的危险因素（OR = 1.673，95%CI = 1.103 - 2.536；OR = 2.171，95%CI = 1.372 - 2.436）。MMP2 rs243865和MMP9 rs3918242多态性与中国人群中RSA风险显著相关。
