title: Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis.
abstract: BACKGROUND
  Congenital heart disease (CHD) is one of the most common birth defects and the leading cause of deaths among individuals with congenital structural abnormalities worldwide. Both Methionine synthase reductase (MTRR) and Methionine synthase (MTR) are key enzymes involved in the metabolic pathway of homocysteine, which are significant in the earlier period embryogenesis, particularly in the cardiac development. Evidence is mounting for the association between MTRR A66G (rs1801394)/MTR A2756G (rs1805087) and the CHD risk, but results are controversial. Therefore, we conducted a meta-analysis integrating case-control and transmitted disequilibrium test (TDT) studies to obtain more precise estimate of the associations of these two variants with the CHD risk.
  
  
  METHODS
  To combine case-control and TDT studies, we used the Catmap package of R software to calculate odds ratios (ORs) and 95% confidence intervals (CIs).
  
  
  RESULTS
  A total of 9 reports were included in the final meta-analysis. Eight of them comprised of 914 cases, 964 controls, and 441 families that were germane to MTRR A66G polymorphism; and 4 reports comprised of 250 cases, 205 controls, and 53 families that were relevant to MTR A2756G polymorphism. The pooled OR for the MTRR 66 G allele versus A allele was 1.35 (95% CI = 1.14-1.59, P<0.001, Pheterogeneity = 0.073). For MTR A2756G, the G allele conferred a pooled OR of 1.10 (95% CI = 0.78-1.57, P = 0.597, Pheterogeneity = 0.173) compared with the A allele. Sensitivity analyses were carried out to asses the effects of each individual study on the pooled OR, indicating the stability of the outcome. Moreover, positive results were also obtained in all subgroups stratified by study type and ethnicity except the subgroup of TDT studies in MTRR A66G variant.
  
  
  CONCLUSIONS
  This meta-analysis demonstrated a suggestive result that the A66G variant in MTRR, but not the A2756G in MTR, may be associated with the increase of CHD risks.
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Bingxi
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ti
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Shen
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Ke
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhenling
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), MOE (Ministry of Education) Key Laboratory of Environment and Health, Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Song
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D016001:Confidence Intervals; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase