Yang Yan1, Lanlan Fang1, Yuxi Li1, Yiping Yu1, Yiran Li1, Jung-Chien Cheng2, Ying-Pu Sun3. 1. Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. 2. Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: jungchien.cheng@gmail.com. 3. Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: syp2008@vip.sina.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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, I2 = 31%), heterozygote (CT vs CC: OR = 1.74, 95% CI = 1.22-2.50, P = 0.003, I2 = 41%) and dominant (TT + CT vs CC: OR = 1.74, 95% CI = 1.23-2.45, P = 0.002, I2 = 40%) genetic models. MMP9 (-1562C>T) in allelic (T vs C: OR = 1.34, 95% CI = 1.08-1.65, P = 0.007, I2 = 0%), heterozygote (CT vs CC: OR = 1.38, 95% CI = 1.06-1.79, P = 0.02, I2 = 0%) and dominant (TT + CT vs CC: OR = 1.41, 95% CI = 1.10-1.82, P = 0.008, I2 = 0%) genetic models were significantly correlated with the RSA risk. CONCLUSIONS: Our meta-analysis results suggest that MMP2 -735T allele and MMP9 -1562T allele have significant association with the risk of RSA.
BACKGROUND: 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. METHODS: 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. RESULTS: 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, I2 = 31%), heterozygote (CT vs CC: OR = 1.74, 95% CI = 1.22-2.50, P = 0.003, I2 = 41%) and dominant (TT + CT vs CC: OR = 1.74, 95% CI = 1.23-2.45, P = 0.002, I2 = 40%) genetic models. MMP9 (-1562C>T) in allelic (T vs C: OR = 1.34, 95% CI = 1.08-1.65, P = 0.007, I2 = 0%), heterozygote (CT vs CC: OR = 1.38, 95% CI = 1.06-1.79, P = 0.02, I2 = 0%) and dominant (TT + CT vs CC: OR = 1.41, 95% CI = 1.10-1.82, P = 0.008, I2 = 0%) genetic models were significantly correlated with the RSA risk. CONCLUSIONS: Our meta-analysis results suggest that MMP2 -735T allele and MMP9 -1562T allele have significant association with the risk of RSA.