title: MTHFRrs1801133 C>T polymorphism is associated with an increased risk of tetralogy of Fallot.
abstract: Abnormal folate metabolism and common variants of folate-metabolizing enzymes have been described as possible risk factors for congenital heart disease (CHD). Two important folate-metabolizing enzymes involved in the folate/homocysteine metabolic pathway are 5,10-methylenetetrahydrofolate reductase (MTHFR) and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1).MTHFRandMTHFD1polymorphisms may be associated with CHD susceptibility. To evaluate the impact ofMTHFRandMTHFD1single-nucleotide polymorphisms (SNPs) on CHD susceptibility, we genotyped functionalMTHFRSNPs rs1801133 C>T, rs1801131 A>C and rs2274976 G>A, andMTHFDSNPs rs2236225 C>T, rs1950902 G>A and rs1076991 A>G in a hospital-based case-control study of 173 tetralogy of Fallot (TOF) cases and 207 non-CHD controls. WhenMTHFRrs1801133 CC homozygote genotype was used as the reference group, the TT genotype was associated with a significantly increased risk for TOF [TT vs. CC: odds ratio (OR)=1.67; 95% confidence interval (CI): 1.01-2.75; P=0.046]. In the recessive model, whenMTHFRrs1801133 CC/CT genotype was used as the reference group, the TT homozygote genotype was associated with a significantly increased risk for TOF (OR=1.81, 95% CI: 1.15-2.84; P=0.010). In conclusion, our findings suggest thatMTHFRrs1801133 C>T polymorphism may play a role in susceptibility for TOF. Large-scale studies with a more rigorous study design including diverse ethnic populations are required to confirm these findings.
authors.affiliation: Department of Cardiothoracic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Jianbing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Cardiothoracic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Ju
authors.initials: J
authors.lastname: Mei
authors.affiliation: Department of Cardiothoracic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Lianyong
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Cardiothoracic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Zhaolei
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Cardiothoracic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Cardiothoracic Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Fangbao
authors.initials: F
authors.lastname: Ding
keywords: 5,10-methylenetetrahydrofolate reductase; congenital heart disease; molecular epidemiology; polymorphisms; tetralogy of Fallot