Jian Liu1, Jing Qi2, Xiao Yu3, Jie Zhu4, Lixia Zhang5, Qin Ning6, Xiaoping Luo7. 1. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Pediatrics, Xiangyang Central Hospital, Xiangyang, China. Electronic address: drliujian@gmail.com. 2. Department of Neurology, Xiangyang Central Hospital, Xiangyang, China. Electronic address: qijingys@126.com. 3. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: yuxiao4249@sina.com. 4. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zjoyjay@163.com. 5. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zhlx1981508@yahoo.com.cn. 6. Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: qning@tjh.tjmu.edu.cn. 7. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: xpluo@tjh.tjmu.edu.cn.
Abstract
AIMS: We investigated the hypothesis that there are interactions between SNPs in folate metabolism pathway genes and environmental risk factors to the etiology of neural tube defects (NTDs). METHOD: In 602 Chinese families, 609 aborted fetus tissues or blood samples were collected from NTD individuals, and 1106 parental blood samples were detected as controls. We analyzed 28 SNPs in 12 folate pathway genes. Folate supplementation, gestational diabetes mellitus (GDM) and medicine administration before and during pregnancy were investigated. Case-parental control study and transmission/disequilibrium tests were performed according to environmental cofactor stratification. RESULTS: Association between 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and NTDs was significant in all stratifications (all P<.05), and synergistic effects of no folate supplementation and GDM were shown on NTD occurrence. 5-Methyltetrahydrofolate-homocysteine methyltransferase (MTHM) 501A>G in case of GDM, and betaine-homocysteine methyltransferase (BHMT) 716G>A in case of no folate supplementation significantly associated with NTDs (both P<.05), whereas the two genotypes alone did not significantly associate with NTDs (both P>.05). CONCLUSIONS: MTHFR 677C>T genotype, especially in case of no folate supplementation and GDM, promotes NTD occurrence. MTHM 501A>G only in case of GDM, and BHMT 716G>A only in case of no folate supplementation contribute to the etiology of NTDs.
AIMS: We investigated the hypothesis that there are interactions between SNPs in folate metabolism pathway genes and environmental risk factors to the etiology of neural tube defects (NTDs). METHOD: In 602 Chinese families, 609 aborted fetus tissues or blood samples were collected from NTD individuals, and 1106 parental blood samples were detected as controls. We analyzed 28 SNPs in 12 folate pathway genes. Folate supplementation, gestational diabetes mellitus (GDM) and medicine administration before and during pregnancy were investigated. Case-parental control study and transmission/disequilibrium tests were performed according to environmental cofactor stratification. RESULTS: Association between 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and NTDs was significant in all stratifications (all P<.05), and synergistic effects of no folate supplementation and GDM were shown on NTD occurrence. 5-Methyltetrahydrofolate-homocysteine methyltransferase (MTHM) 501A>G in case of GDM, and betaine-homocysteine methyltransferase (BHMT) 716G>A in case of no folate supplementation significantly associated with NTDs (both P<.05), whereas the two genotypes alone did not significantly associate with NTDs (both P>.05). CONCLUSIONS:MTHFR 677C>T genotype, especially in case of no folate supplementation and GDM, promotes NTD occurrence. MTHM 501A>G only in case of GDM, and BHMT 716G>A only in case of no folate supplementation contribute to the etiology of NTDs.
Authors: Inna Dubchak; Sandhya Balasubramanian; Sheng Wang; Meydan Cem; Cem Meyden; Dinanath Sulakhe; Alexander Poliakov; Daniela Börnigen; Bingqing Xie; Andrew Taylor; Jianzhu Ma; Alex R Paciorkowski; Ghayda M Mirzaa; Paul Dave; Gady Agam; Jinbo Xu; Lihadh Al-Gazali; Christopher E Mason; M Elizabeth Ross; Natalia Maltsev; T Conrad Gilliam Journal: PLoS One Date: 2014-12-15 Impact factor: 3.240
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