Genetic variation in folate metabolism is associated with the risk of conotruncal heart defects in a Chinese population

Xike Wang,Haitao Wei,Yue Wu,Ying Tian,Lei Luo

doi:10.1186/s12887-018-1266-9

Xike Wang, Haitao Wei + Show 3 more

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https://doi.org/10.1186/s12887-018-1266-9

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Journal: BMC Pediatrics	Publication Date: Aug 30, 2018
Citations: 7	License type: open-access

Affiliation: Guizhou Provincial People's Hospital

Abstract

BackgroundConotruncal heart defects (CTDs) are a subgroup of congenital heart defects that are considered to be the most common type of birth defect worldwide. Genetic disturbances in folate metabolism may increase the risk of CTDs.MethodsWe evaluated five single-nucleotide polymorphisms (SNPs) in genes related to folic acid metabolism: methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), solute carrier family 19, member 1 (SLC19A1 G80A), methionine synthase (MTR A2576G), and methionine synthase reductase (MTRR A66G), as risk factors for CTDs including various types of malformation, in a total of 193 mothers with CTD-affected offspring and 234 healthy controls in a Chinese population.ResultsLogistic regression analyses revealed that subjects carrying the TT genotype of MTHFR C677T, the C allele of MTHFR A1298C, and the AA genotype of SLC19A1 G80A had significant 2.47-fold (TT vs. CC, OR [95% CI] = 2.47 [1.42–4.32], p = 0.009), 2.05–2.20-fold (AC vs. AA, 2.05 [1.28–3.21], p = 0.0023; CC vs AA, 2.20 [1.38–3.58], p = 0.0011), and 1.68-fold (AA vs. GG, 1.68 [1.02–2.70], p = 0.0371) increased risk of CTDs, respectively. Subjects carrying both variant genotypes of MTHFR A1298C and SLC19A1 G80A had a higher (3.23 [1.71–6.02], p = 0.0002) increased risk for CTDs. Moreover, the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms were found to be significantly associated with the risk of certain subtypes of CTD.ConclusionsOur data suggest that maternal folate-related SNPs might be associated with the risk of CTDs in offspring.

Highlights

Conotruncal heart defects (CTDs) are a subgroup of congenital heart defects that are considered to be the most common type of birth defect worldwide
Our results demonstrated that genotypes for methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, and Solute carrier family 19 (SLC19A1) G80A might be associated with the risk of
The results showed that the Methionine synthase reductase (MTRR) 66G allele significantly increased the risk of Congenital heart defect (CHD) compared with the MTRR 66A allele (OR: 1.35, 95% confidence interval (CI): 1.14–1.59, p < 0.001), but no significant differences were found in the Methionine synthase (MTR) A2576G polymorphism between the groups

Summary

Introduction

Conotruncal heart defects (CTDs) are a subgroup of congenital heart defects that are considered to be the most common type of birth defect worldwide. Genetic disturbances in folate metabolism may increase the risk of CTDs. Congenital heart defects (CHDs) are the most common type of birth defect and are associated with significant morbidity and mortality. Among the identified subgroups of CHDs, conotruncal heart defects (CTDs) account for 25–33% of all patients [4] This CHD subgroup involves cardiac structures that are partially derived from cell lineages [5], and includes. The MTHFR C677T variant (TT), MTHFR A1298C variant (CC), SLC19A1 G80A variant (AG or AA), MTR A2576G variant (GG), and MTRR A66G variant (GG) have been extensively investigated These gene variants would theoretically influence the risk of CHD/CTD, studies have yielded conflicting results on this issue in different populations [10, 12, 15,16,17,18,19]

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