caa a22 4500 606235582 CHVBK 20210128101243.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s11010-015-2453-8 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2453-8 Functional variant in methionine synthase reductase intron-1 is associated with pleiotropic congenital malformations [Elektronische Daten] [Haiqin Cheng, Huili Li, Zhaoli Bu, Qin Zhang, Baoling Bai, Hong Zhao, Ren-Ke Li, Ting Zhang, Jun Xie] Congenital malformations, such as neural tube defects (NTDs) and congenital heart disease (CHD), cause significant fetal mortality and childhood morbidity. NTDs are a common congenital anomaly, and are typically induced by higher maternal homocysteine (Hcy) levels and abnormal folate metabolism. The gene encoding methionine synthase reductase (MTRR) is essential for adequate remethylation of Hcy. Previous studies have focused on the coding region of genes involved in one-carbon metabolism, but recent research demonstrates that an allelic change in a non-coding region of MTRR (rs326119) increases the risk of CHD. We hypothesized that this variant might contribute to the etiology of NTDs as well, based on a common role during early embryogenesis. In the present study, 244 neural tube defect cases and 407 controls from northern China were analyzed to determine any association (by χ 2 test) between rs326119 and disease phenotypes. Significant increased risk of anencephaly was seen in MTRR variant rs326119 heterozygote (het) and homozygote (hom) individuals [odds ratios (OR)het=1.81; ORhom=2.05)]. Furthermore, this variant was also a risk factor for congenital malformations of the adrenal gland (OR=1.85), likely due to multiple systemic malformations in the NTDs case population. Our present data indicate that the rs326119 non-coding variant of MTRR has a pleiotropic effect on the development of multiple tissues, especially during early stages in utero. This suggests the allelic state of MTRR is a significant clinical factor affecting Hcy levels and optimal folic supplementation. Springer Science+Business Media New York, 2015 Congenital malformations nationallicence Neural tube defects nationallicence MTRR nationallicence MTR nationallicence Single nucleotide polymorphism nationallicence Folic acid nationallicence Cheng Haiqin Department of Biochemistry and Molecular Biology, Ministry of Education Key Laboratory of Cellular Physiology, Shanxi Medical University, 030001, Taiyuan, Shanxi, China aut Li Huili Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, 100020, Beijing, China aut Bu Zhaoli Department of Biochemistry and Molecular Biology, Ministry of Education Key Laboratory of Cellular Physiology, Shanxi Medical University, 030001, Taiyuan, Shanxi, China aut Zhang Qin Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, 100020, Beijing, China aut Bai Baoling Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, 100020, Beijing, China aut Zhao Hong Department of Biochemistry and Molecular Biology, Ministry of Education Key Laboratory of Cellular Physiology, Shanxi Medical University, 030001, Taiyuan, Shanxi, China aut Li Ren-Ke Toronto General Research Institute, University Health Network, Toronto, Canada aut Zhang Ting Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, 100020, Beijing, China aut Xie Jun Department of Biochemistry and Molecular Biology, Ministry of Education Key Laboratory of Cellular Physiology, Shanxi Medical University, 030001, Taiyuan, Shanxi, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 51-56 0300-8177 407:1-2<51 2015 407 11010 https://doi.org/10.1007/s11010-015-2453-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2453-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cheng Haiqin Department of Biochemistry and Molecular Biology, Ministry of Education Key Laboratory of Cellular Physiology, Shanxi Medical University, 030001, Taiyuan, Shanxi, China aut NATIONALLICENCE 700 1- Li Huili Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, 100020, Beijing, China aut NATIONALLICENCE 700 1- Bu Zhaoli Department of Biochemistry and Molecular Biology, Ministry of Education Key Laboratory of Cellular Physiology, Shanxi Medical University, 030001, Taiyuan, Shanxi, China aut NATIONALLICENCE 700 1- Zhang Qin Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, 100020, Beijing, China aut NATIONALLICENCE 700 1- Bai Baoling Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, 100020, Beijing, China aut NATIONALLICENCE 700 1- Zhao Hong Department of Biochemistry and Molecular Biology, Ministry of Education Key Laboratory of Cellular Physiology, Shanxi Medical University, 030001, Taiyuan, Shanxi, China aut NATIONALLICENCE 700 1- Li Ren-Ke Toronto General Research Institute, University Health Network, Toronto, Canada aut NATIONALLICENCE 700 1- Zhang Ting Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, 100020, Beijing, China aut NATIONALLICENCE 700 1- Xie Jun Department of Biochemistry and Molecular Biology, Ministry of Education Key Laboratory of Cellular Physiology, Shanxi Medical University, 030001, Taiyuan, Shanxi, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 51-56 0300-8177 407:1-2<51 2015 407 11010