Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Gene. 2021 Jan 30;767:145173. doi: 10.1016/j.gene.2020.145173. Epub 2020 Sep 29.
Recurrent spontaneous abortion (RSA) accounts for the most common complication of early pregnancy in humans. Matrix metalloproteinases (MMPs) play important regulatory roles in implantation and placentation to ensure a successful pregnancy. Single nucleotide polymorphisms (SNPs) have been identified in the promoters of MMP2 and MMP9 genes. However, the associations between MMP2 and MMP9 SNPs and the RSA risk remain unclear. The aim of this meta-analysis was to investigate whether MMP2 (-735C>T) and MMP9 (-1562C>T) SNPs are associated with the risk of RSA.
Literatures published before 17th April 2020 were screened to identify the eligible studies. Heterogeneity, sensitivity and publication bias analysis were analyzed by the STATA software. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Review Manager software with fixed effects model.
After screening, 2 studies for MMP2 (-735C>T) (278 RSA cases and 265 controls) and 4 studies for MMP9 (-1562C>T) (520 RSA cases and 512 controls) were enrolled in this meta-analysis. Results showed that MMP2 (-735C>T) presented a statistically significant association with the risk of RSA under allelic (T vs C: OR = 1.50, 95% CI = 1.14-1.98, P = 0.004, I = 31%), heterozygote (CT vs CC: OR = 1.74, 95% CI = 1.22-2.50, P = 0.003, I = 41%) and dominant (TT + CT vs CC: OR = 1.74, 95% CI = 1.23-2.45, P = 0.002, I = 40%) genetic models. MMP9 (-1562C>T) in allelic (T vs C: OR = 1.34, 95% CI = 1.08-1.65, P = 0.007, I = 0%), heterozygote (CT vs CC: OR = 1.38, 95% CI = 1.06-1.79, P = 0.02, I = 0%) and dominant (TT + CT vs CC: OR = 1.41, 95% CI = 1.10-1.82, P = 0.008, I = 0%) genetic models were significantly correlated with the RSA risk.
Our meta-analysis results suggest that MMP2 -735T allele and MMP9 -1562T allele have significant association with the risk of RSA.
复发性自然流产（RSA）是人类早期妊娠最常见的并发症。基质金属蛋白酶（MMPs）在胚胎着床和胎盘形成中发挥着重要的调控作用，以确保妊娠的成功。MMP2 和 MMP9 基因启动子中已发现单核苷酸多态性（SNPs）。然而，MMP2 和 MMP9 SNPs 与 RSA 风险之间的关联仍不清楚。本荟萃分析的目的是研究 MMP2（-735C>T）和 MMP9（-1562C>T）SNP 是否与 RSA 风险相关。
筛选截止到 2020 年 4 月 17 日之前发表的文献，以确定符合条件的研究。采用 STATA 软件分析异质性、敏感性和发表偏倚。采用 Review Manager 软件的固定效应模型计算比值比（ORs）和 95%置信区间（CIs）。
经过筛选，本荟萃分析纳入了 2 项 MMP2（-735C>T）（278 例 RSA 病例和 265 例对照）和 4 项 MMP9（-1562C>T）（520 例 RSA 病例和 512 例对照）的研究。结果表明，MMP2（-735C>T）在等位基因（T 对 C：OR=1.50，95%CI=1.14-1.98，P=0.004，I=31%）、杂合子（CT 对 CC：OR=1.74，95%CI=1.22-2.50，P=0.003，I=41%）和显性（TT+CT 对 CC：OR=1.74，95%CI=1.23-2.45，P=0.002，I=40%）遗传模型中与 RSA 风险显著相关。MMP9（-1562C>T）在等位基因（T 对 C：OR=1.34，95%CI=1.08-1.65，P=0.007，I=0%）、杂合子（CT 对 CC：OR=1.38，95%CI=1.06-1.79，P=0.02，I=0%）和显性（TT+CT 对 CC：OR=1.41，95%CI=1.10-1.82，P=0.008，I=0%）遗传模型中与 RSA 风险显著相关。
本荟萃分析结果表明，MMP2-735T 等位基因和 MMP9-1562T 等位基因与 RSA 风险显著相关。
