Association of maternal methionine synthase reductase gene polymorphisms with the risk of congenital heart disease in offspring: a hospital-based case-control study.

BACKGROUND: Evidence suggests that periconceptional folic acid supplementation may prevent congenital heart disease (CHD). Methionine synthase reductase (MTRR) is one of the key regulatory enzymes in the folate metabolic pathway. This study aimed to comprehensively evaluate the association of single nucleotide polymorphisms (SNPs) in the maternal MTRR gene with CHD risk in offspring. METHODS: A hospital-based case-control study involving 740 mothers of CHD cases and 683 health controls was conducted. RESULTS: The study showed that maternal MTRR gene polymorphisms at rs1532268 (C/T vs. C/C: aOR = 1.524; T/T vs. C/C: aOR = 3.178), rs1802059 (G/A vs. G/G: aOR = 1.410; A/A vs. G/G: aOR = 3.953), rs2287779 (G/A vs. G/G: aOR = 0.540), rs16879334 (C/G vs. C/C: aOR = 0.454), and rs2303080 (T/A vs. T/T: aOR = 0.546) were associated with the risk of CHD. And seven haplotypes were observed to be associated with the risk of CHD, T-G-A haplotype (OR = 1.298), C-A-C-C (OR = 4.824) and A-G haplotype (OR = 1.751) were associated with increased risk of CHD in offspring; A-A-A (OR = 0.773), T-A-A (OR = 0.557), G-A-C-C (OR = 0.598) and G-C (OR = 0.740) were associated with decreased risk of CHD in offspring. CONCLUSIONS: Maternal MTRR gene polymorphisms were associated with CHD in offspring, and its haplotypes have affected the occurrence of CHD. Furthermore, given the complexity and heterogeneity of CHD, the mechanisms by which these factors influence offspring cardiac development remain unknown, and studies in larger samples in an ethnically diverse population are needed.

Association of methylenetetrahydrofolate reductase gene polymorphisms and maternal folic acid use with the risk of congenital heart disease.

Background: To systematically evaluate the association of MTHFR genetic polymorphisms, maternal folic acid intake, and the time when folic acid intake was started with the risk of congenital heart disease (CHD) and investigated the role of their interaction on infant CHD risk in Chinese populations. Methods: A case-control study involving 592 CHD cases, 617 health controls, and their mothers was performed. The exposures of interest were single nucleotide polymorphisms (SNPs) of the MTHFR gene, maternal folic acid use, and the time when folic acid use was started. We applied the logistic regression model to explore the strength of association. Results: Our findings showed that mothers lacking folic acid intake had a significantly higher risk of CHD in offspring (aOR = 2.00; 95%CI: 1.34-2.98). Mothers who started to use folic acid from the first trimester of the fetation (aOR = 1.65; 95% CI: 1.22-2.23) or from the second trimester of the fetation (aOR = 7.77; 95% CI: 2.52-23.96), compared with those starting to use folic acid from 3 months previous to the conception, were at a significantly higher risk of CHD in offspring. Genetic variants at rs2066470 (AA vs. GG: aOR = 5.09, 95%CI: 1.99-13.03), rs1801133 (AA vs. GG: aOR = 2.49, 95%CI: 1.58-3.93), and rs1801131 (TG vs. TT: aOR = 1.84, 95%CI: 1.36-2.50; GG vs. TT: aOR = 3.58, 95%CI: 1.68-7.63) were significantly associated with the risk of CHD based on the multivariate analysis. Additionally, statistically significant interactions between maternal folic acid intake and genetic variants of the MTHFR gene at rs1801133 and rs1801131 were observed. Conclusion: An association of maternal folic acid intake and the time when intake was started with the risk of CHD in offspring was found. What's more, maternal folic acid fortification may help counteract partial of the risks of CHD in offspring attributable to MTHFR genetic mutations. Registration number: http://www.chictr.org.cn/edit.aspx?pid=28300&htm=4, identifier: ChiCTR1800016635.

Association of polymorphisms of FOLR1 gene and FOLR2 gene and maternal folic acid supplementation with risk of ventricular septal defect: a case-control study.

OBJECTIVES: It was the first time to examine the role of maternal polymorphisms of FOLR1 gene and FOLR2 gene, as well as their interactions with maternal folic acid supplementation (FAS), in the risk of ventricular septal defect (VSD). METHODS: A case-control study was conducted with 385 mothers of VSD infants and 652 controls. The exposures of interest were FAS and FOLR1 gene and FOLR2 gene polymorphisms. The logistic regression model was used for accessing the strength of association. RESULTS: After controlling for the potential confounders, women who did not utilize folic acid had a substantially higher risk of VSD (aOR = 2.25; 95% CI: 1.48 to 3.43), compared to those who did. We also observed genetic polymorphisms of FOLR1 gene at rs2071010 (GA vs. GG: aOR = 0.63, 95%CI: 0.45 to 0.88) and rs11235462 (AA vs. TT: aOR = 0.53, 95%CI: 0.33 to 0.84), as well as FOLR2 gene at rs651646 (AA vs. TT: aOR = 0.46, 95%CI: 0.30 to 0.70), rs2298444 (CC vs. TT: aOR = 0.58, 95%CI: 0.36 to 0.91) and rs514933 (TC vs. TT: aOR = 0.57, 95%CI: 0.41 to 0.78) were associated with a lower risk of VSD. Furthermore, there was a statistically significant interaction between maternal FAS and genetic polymorphisms at rs514933 on the risk of VSD (FDR_P = 0.015). CONCLUSIONS: The maternal genetic polymorphisms of the FOLR1 gene and FOLR2 gene, as well as FAS and their interactions, were shown to be significantly associated with the risk of VSD in offspring.

Hyperbaric-Oxygen Therapy Improves Survival and Functional Outcome of Acute Severe Intracerebral Hemorrhage.

BACKGROUND: Prognosis of spontaneous intracerebral hemorrhage (ICH) remains poor worldwide. AIMS OF THE STUDY: To investigate the effect and optimal protocol for hyperbaric-oxygen therapy (HBOT), and reduce incidence of upper gastrointestinal bleeding (UGIB) in ICH. METHODS: This prospective, randomized, controlled trial included 565 patients with acute severe ICH. Participants were randomly assigned to a sham-control group (Group A) and four intervention groups: Groups B and C with 2.0 atmospheres absolute (ATA) pressure and HBOT exposure for 60 or 90 sessions, respectively; and Groups D and E with 1.5 ATA for 60 or 90 sessions, respectively. All patients received emergency craniotomy with hematoma evacuation. Outcome measures were modified Barthel Index (MBI) and modified Rankin Scale (mRS) scores, mortality rates at follow-up six months. UGIB rates were assessed as potential side effect. RESULTS: In four intervention groups, MBI and mRS scores were all significantly improved, and mortality rates were all significantly decreased compared with Group A (all p < 0.005). UGIB rates were 39.25, 60.00, 64.49, 36.79, and 34.26% in Groups A, B, C, D, and E, respectively. UGIB rates in Groups B and C were significantly increased compared with Groups A, D and E (all p < 0.005). None of UGIB were clinically significant. CONCLUSIONS: HBOT significantly improves survival and functional outcomes of ICH. HBOT at 1.5 and 2.0 ATA had the same beneficial effect. A pressure of 1.5 ATA and 60 HBOT exposures represents an optimal protocol for HBOT. Further studies are needed to optimize the protocol per specific patient.