Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis.
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 p...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3942359?pdf=render |
| _version_ | 1818925104743055360 |
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| author | Bingxi Cai Ti Zhang Rong Zhong Li Zou Beibei Zhu Wei Chen Na Shen Juntao Ke Jiao Lou Zhenling Wang Yu Sun Lifeng Liu Ranran Song |
| author_facet | Bingxi Cai Ti Zhang Rong Zhong Li Zou Beibei Zhu Wei Chen Na Shen Juntao Ke Jiao Lou Zhenling Wang Yu Sun Lifeng Liu Ranran Song |
| author_sort | Bingxi Cai |
| collection | DOAJ |
| description | 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. |
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| language | English |
| last_indexed | 2024-12-20T02:35:55Z |
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| spelling | doaj.art-1507392a641243c883abb96332a4281f2022-12-21T19:56:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e8960910.1371/journal.pone.0089609Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis.Bingxi CaiTi ZhangRong ZhongLi ZouBeibei ZhuWei ChenNa ShenJuntao KeJiao LouZhenling WangYu SunLifeng LiuRanran SongBACKGROUND: 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.http://europepmc.org/articles/PMC3942359?pdf=render |
| spellingShingle | Bingxi Cai Ti Zhang Rong Zhong Li Zou Beibei Zhu Wei Chen Na Shen Juntao Ke Jiao Lou Zhenling Wang Yu Sun Lifeng Liu Ranran Song Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis. PLoS ONE |
| title | Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis. |
| title_full | Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis. |
| title_fullStr | Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis. |
| title_full_unstemmed | Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis. |
| title_short | Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis. |
| title_sort | genetic variant in mtrr but not mtr is associated with risk of congenital heart disease an integrated meta analysis |
| url | http://europepmc.org/articles/PMC3942359?pdf=render |
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