Association between Fetal MTHFR A1298C (rs1801131) Polymorphism and Neural Tube Defects Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: The association of the fetal MTHFR A1298C (rs1801131) polymorphism and neural tube defects (NTDs) susceptibility has been widely demonstrated, but the results remain inconclusive. Thus, we performed a meta-analysis to investigate the association between fetal MTHFR A1298C polymorphism and NTDs risk. METHODS: An electronic search of PubMed, web of science, SciELO, CNKI database for studies on the fetal MTHFR A1298C polymorphism and NTDs risk was performed up to March 30, 2020. RESULTS: A total of 22 case-control studies with 3,224 fetuses with NTDs and 3,295 controls were selected. Overall, pooled data showed that the fetal MTHFR A1298C polymorphism was not significantly associated with risk an increased risk of NTDs in the global population. When stratified analysis by ethnicity, country of origin and NTDs type, still no statistically significant association was found. CONCLUSIONS: Our pooled data emerged no evidence for significant association between fetal MTHFR A1298C polymorphism and NTDs risk.

Association of Fetal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects: A Systematic Review and Update Meta-Analysis.

Background MTHFR gene may be a key epigenetic regulation-related factor crucial during embryogenesis. We performed a meta-analysis to determine the association of fetal MTHFR C677T polymorphism with neural tube defects (NTDs).Methods A comprehensive literature search of the PubMed, Embase, and CNKI database was performed up to April 10, 2020.Results A total of 19 case-control studies with 2,228 NTDs cases and 4,220 controls were identified. Pooled data revealed that the fetal MTHFR C677T polymorphism was significantly highly correlated with development of NTDs in the overall population. Stratified analysis showed a significant association among Caucasians and Asians, but not in mixed populations. There was a significant association between the MTHFR C677T polymorphism and spina bifida risk. No publication bias was found under any genetic model.Conclusions Our pooled data support the fetal MTHFR C677T polymorphism association with risk of NTDs, especially among Caucasians and Asians.

Cumulative Evidence for Association of IL-10 -1082G > A Polymorphism with Susceptibility to Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis.

BACKGROUND: The IL-10 -1082 G > A polymorphism has been reported to be associated with a risk of recurrent pregnancy loss (RPL) with inconsistent results. Thus, to clarify the effect of the polymorphism on the susceptibility to RPL, a meta-analysis was performed. Methods: A systematic literature search in PubMed, Web of Science, Scopus and SciELO was performed to identify the relevant studies published up to December 20, 2019, and related information was extracted. Results: A total of 17 case-control studies with 3,224 RPL cases and 3,295 controls were selected. Pooled data revealed that IL-10 -1082 G > A polymorphism was significantly associated with risk of RPL in the global population. Moreover, subgroup analysis indicated a significant association in Caucasians, but not in Asian or mixed populations. Conclusions: Our pooled data highlights that IL-10 -1082 G > A polymorphism is a risk factor for RPL susceptibility in the global population, especially in Caucasians.

Association of Endothelial Nitric Oxide Synthase 894G > T Polymorphism with Preeclampsia Risk: A Systematic Review and Meta-Analysis based on 35 Studies.

BACKGROUND: Several case-control studies have been performed to investigate the association between 894 G > T polymorphism in endothelial nitric oxide synthase (eNOS) gene and susceptibility to preeclampsia. However, the results were inconsistent and inconclusive. Therefore, we conducted this meta-analysis to investigate the association. Methods: All studies published up to September 30, 2019 were identified by searching electronic databases such as PubMed, EMBASE, CNKI, and WANFANG. Results: A total of 35 case- control studies with 4,254 cases and 5,801 controls were selected. There was a significant association between the eNOS 894 G > T and preeclampsia risk. When stratified by ethnicity, an increased risk of preeclampsia was found in Caucasian and Mixed populations, but not in Asians or Africans. Conclusion: Based on our meta-analysis, the eNOS 894 G > T polymorphism was associated with an increased risk of preeclampsia, especially among Caucasian and Mixed populations.

Association of MMP-2, MMP-3, and MMP-9 Polymorphisms with Susceptibility to Recurrent Pregnancy Loss.

BACKGROUND: Genetic causes that contribute to recurrent pregnancy loss (RPL) are not fully understood. The aim of this study was to evaluate the association of five polymorphisms at MMP-2, MMP-3, and MMP-9 genes with risk of RPL. Methods: The study comprised 250 women with RPL and 250 healthy controls. The MMP-2 (rs243865, rs2285053), MMP-3 (rs35068180), and MMP 9 (rs3918242, rs17576) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: A significant association was found between MMP-3 rs35068180 polymorphism and RPL risk. There was no significant association between RPL and polymorphisms at MMP-2 (rs243865, rs2285053) and MMP 9 (rs3918242, rs17576) genes. Conclusion: MMP-3 rs35068180 polymorphism may modulate RPL risk in Iranian women. There is no evidence to suggest that MMP-2 (rs243865, rs2285053) and MMP 9 (rs3918242, rs17576) polymorphisms are associated with RPL risk.

Association of Insulin-like Growth Factor-II Apa1 and MspI Polymorphisms with Intrauterine Growth Restriction Risk.

BackgroundInsulin-like growth factor-II (IGF-II) has a prominent role in fetal growth and development. The aim of this study was to investigate the association of IGF-II Apa1 and MspI polymorphisms with intrauterine growth restriction (IUGR) risk. Methods: A total of 45 infants with IUGR and 45 infants appropriate for gestational (AGA) were enrolled. Genotyping of Apa1 and MspI polymorphisms was assayed by PCR-RFLP approach. Results: The heterozygote genotype (AG) of IGF-II Apa1 CT was associated with an increased risk of IUGR. Genotypes and alleles of IGF-II MspI polymorphism had no significant association with IUGR susceptibility (P > 0.05). Conclusions: The current study suggests that IGF-II Apa1 polymorphism is associated with an increased risk of IUGR, while IGF-II MspI showed no association with IUGR. Thus, IGF-II Apa1 polymorphism could be used as a relevant molecular marker to identify the fetus at risk of developing IUGR.

Association of IL-12B rs3212227 and IL-6 rs1800795 Polymorphisms with Susceptibility to Cervical Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Primary studies have shown that the IL-12B rs3212227 and IL-6 rs1800795 polymorphisms are associated with an increased risk of cervical cancer. However, conflicting results warrant a meta-analysis to obtain more precise estimates. METHODS: A comprehensive literate search on PubMed, Web of Science, Scopus, CNKI, and SciELO was performed to collect all eligible studies up to November 10, 2019. The pooled odds ratios (OR) and 95% confidence intervals (CI) were used to calculate the risk. This meta-analysis was carried out by utilizing CMA software. RESULTS: A total of eleven case-control studies including four studies on IL-12B rs3212227 and seven studies on IL-6 rs1800795 were selected. Pooled ORs revealed that the IL-6 rs1800795 polymorphism was significantly associated with an increased risk of cervical cancer (C vs. G: OR = 1.294, 95% CI 1.071-1.564, p= 0.007; CC vs. GG: OR = 1.633, 95% CI 1.059-2.520, p= 0.027; CC+CG vs. GG: OR = 1.312, 95% CI 1.048-1.643, p= 0.018; and CC vs. CG+GG: OR = 1.592, 95% CI 1.268-1.999, p≤0.001), but not IL-12B rs3212227 polymorphism. Stratified analysis by ethnicity revealed that both IL-12B rs3212227 and IL-6 rs1800795 polymorphisms were associated with risk of cervical cancer in Asian women. CONCLUSIONS: Our pooled data revealed that the IL-12B rs3212227 and IL-6 rs1800795 polymorphisms may be used to identify individuals at high risk of cervical cancer in Asian women.
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Association of XRCC3 18067 C>T (Thr241Met) polymorphism with risk of cervical and ovarian cancers: A systematic review and meta-analysis.

The 18067 C>T polymorphism of XRCC3 gene has been considered to be implicated in the development of cervical and ovarian cancers, but the results are inconsistent. Thus, we conducted a meta-analysis to assess the association of XRCC3 18067 C>T polymorphism with risk of cervical and ovarian cancers. All studies on the association of XRCC3 18067 C>T polymorphism with cervical and ovarian cancers risk were retrieved. Finally, a total of 17 studies including 10 studies with 5,637 cases and 10,057 controls on ovarian cancer and 7 studies with 1,112 cases and 1,233 controls on cervical cancer were selected. Overall, pooled results showed that the XRCC3 18067 C>T polymorphism was significantly associated with increased risk of ovarian cancer (TC vs. CC: OR = 0.904, 95% CI = 0.841-0.972, p = 0.006; TT + TC vs. CC: OR = 0.914, 95% CI = 0.853-0.979, p = 0.010) and cervical cancer (TC vs. CC: OR = 1.00, 95% CI = 1.066-1.585, p = 0.009). Further subgroup analysis by ethnicity revealed an increased risk of cervical and ovarian cancer in Asians and Caucasians, respectively. The present meta-analysis inconsistent with the previous meta-analysis suggests that the XRCC3 18067 C>T polymorphism might be implicated in the pathogenesis of cervical and ovarian cancers.

Association of Promoter Region Polymorphisms of IL-6 and IL-18 Genes with Risk of Recurrent Pregnancy Loss: A Systematic Review and Meta-Analysis.

Background: The present meta-analysis was performed to investigate the association of promoter region polymorphisms at IL-6 and IL-18 genes with recurrent pregnancy loss (RPL) risk. Methods: An electronic search of the PubMed, Embase, ISI Web of Knowledge and CNKI databases was performed to identify eligible studies up to May 30, 2019. Results: A total of 31 case-control studies were finally selected. Significant associations with the risk of RPL were detected for the IL-6 -174 G > C, -634 G > C and IL-18 -137 G > C polymorphisms in overall population. Further, subgroup analyses by ethnicity revealed that the IL-6 -174 G > C and -634 G > C polymorphisms were significantly associated with risk of RPL risk in Asians. Conclusions: Our results suggest that the IL-6 -174 G > C, -634 G > C and IL-18 -137 G > C polymorphisms may contribute to the susceptibility of RPL. The IL-18 -607 C > A polymorphism does not appear to influence the development of RPL.

Association of IL-6 -176G > C Polymorphism with Susceptibility to Preeclampsia: A Systematic Review and Meta-Analysis.

Background: Many studies have described the influence of -176G > C polymorphism of the IL-6 gene on susceptibility to preeclampsia. However, the results have remained inconclusive and controversial. Therefore, we performed a meta-analysis to more precisely determine the association between the IL-6 -176G > C polymorphism and preeclampsia risk. Methods: Electronic databases including PubMed, Embase, Web of Science, and CNKI were searched up to August 15, 2019. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to calculate the association. Results: A total of 12 studies with 1,821 preeclampsia cases and 3,339 controls were selected. Overall, no significant association was found between IL-6 -176G > C polymorphism and preeclampsia risk. In the stratified analyses by ethnicity, there was a significant association in Asians, but not in Caucasians and mixed populations. Conclusions: The results of meta-analysis indicated that IL-6 -176G > C polymorphism was not significantly associated with risk of preeclampsia in overall population.

Association of Interleukin-10 -1082G > A Polymorphism with Susceptibility to Preeclampsia: A Systematic Review and Meta-Analysis Based on 21 Studies.

Background: Previous studies have reported the association between IL-10 -1082 G > A polymorphism and preeclampsia risk, but the results remained controversial. Therefore, this meta-analysis was performed to evaluate the association of IL-10 -1082 G > A polymorphism with preeclampsia risk.Methods: We searched PubMed, ISI Web of Knowledge and CNKI databases to identify eligible studies up to September 05, 2019.Results: A total of 21 case-control studies with 3,510 cases and 5,874 controls were selected. The results revealed that IL-10 -1082 G > A polymorphism was significantly associated with an increased risk of preeclampsia under the recessive model (AA vs. AG + GG: OR = 1.191, 95% CI = 1.018-1.394, P = 0.029). Stratified analyses by ethnicity revealed a significantly increased risk of preeclampsia in Asian and mixed populations, but not in Caucasians. Moreover, there was a significant association among Chinese and Brazilian.Conclusions: Our results showed that IL-10 -1082 G > A polymorphism was significantly associated with an increased risk of preeclampsia.

Association of MTHFR 677C>T Polymorphism with Susceptibility to Ovarian and Cervical Cancers: A Systematic Review and Meta-Analysis.

Background: Previous studies have evaluated the impact of MTHFR 677C>T polymorphism on susceptibility to ovarian and cervical cancers in women, but the conclusions are still controversial. To get a more precise evaluation of the association between MTHFR 677C>T polymorphism and risk of ovarian and cervical cancers, we performed a meta-analysis of the association of all eligible studies. Methods: A comprehensive search performed in PubMed, Google Scholar, CNKI, and Web of Science databases to identify the relevant studies up to October 15, 2018. The strength of the association was estimated by odds ratios (OR) with 95% confidence interval (CI). Results: A total of 27 case-control studies including eleven studies with 4990 cases 7730 controls on ovarian cancer and 16 studies with 4990 cases and 7730 controls on cervical cancer were selected. Pooled data revealed that the MTHFR 677C>T polymorphism not significantly associated with an increased risk of ovarian and cervical cancers under all five genetic models. However, stratified analysis by ethnicity showed that the MTHFR 677C>T polymorphism was significantly associated with risk of ovarian cancer in Asians. No publication bias was found in the current meta-analysis. Conclusions: The results of this meta-analysis proposes that the MTHFR 677C>T polymorphism may not play a role in development of ovarian and cervical cancers in overall population. Further well-designed studies are necessary to clarify the precise role of the MTHFR 677C>T polymorphism on ovarian and cervical cancers risk.