title: Association of MTHFR A1298C polymorphism with conotruncal heart disease.
abstract: Congenital heart diseases are common congenital anomalies with 1% prevalence worldwide and are associated with significant childhood morbidity and mortality. Among a wide range of aetiologically heterogeneous conditions, conotruncal anomalies account for approximately one-third of all congenital heart defects. The aetiology of conotruncal heart diseases is complex, with both environmental and genetic causes. Hyperhomocysteinaemia, which is often accompanied by the defects of folic acid metabolism, is known to cause conotruncal heart anomalies. In this study, we have evaluated three polymorphisms in the following two hyperhomocysteinaemia-related genes: methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and nicotinamide N-methyl transferase (NNMT rs694539) in 79 children with conotruncal heart disease and 99 children without conotruncal heart disease. Genotype distribution of the MTHFR A1298C polymorphism showed a statistically significant difference between the two groups. In the case group, AC and CC genotypes were higher than the control group (p<0.05). We have found that MTHFR A1298C polymorphism is associated with conotruncal heart disease; C allele (p=0.028), AC (OR[95% CI]=2.48[1.24-4.95], p=0.010), CC (OR[95% CI]=3.01[1.16-7.83], p=0.023), and AC+CC (OR[95% CI]=2.60[1.36-4.99], p=0.004) genotypes are more frequent in the patient group. Genotype distributions of the MTHFR C677T and NNMT rs694539 polymorphisms were similar in the two groups when evaluated separately and also according to the dominant genetic model (p>0.05). Our results suggest that MTHFR 1298C allele is a risk factor for conotruncal heart disease.
authors.affiliation: 1Faculty of Medicine,Department of Medical Genetics,Kirikkale University,Kirikkale,Turkey.
authors.forename: Beyza D
authors.initials: BD
authors.lastname: Sayin Kocakap
authors.affiliation: 2Department of Pediatric Cardiology, Faculty of Medicine,Kirikkale University,Kirikkale,Turkey.
authors.forename: Cihat
authors.initials: C
authors.lastname: Sanli
authors.affiliation: 1Faculty of Medicine,Department of Medical Genetics,Kirikkale University,Kirikkale,Turkey.
authors.forename: Feryal
authors.initials: F
authors.lastname: Cabuk
authors.affiliation: 3Department of Cardiovascular Surgery,Ankara Dr Sami Ulus Obstetrics and Gynecology,Children's Health and Diseases Training and Research Hospital,Ankara,Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Koc
authors.affiliation: 3Department of Cardiovascular Surgery,Ankara Dr Sami Ulus Obstetrics and Gynecology,Children's Health and Diseases Training and Research Hospital,Ankara,Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Kutsal
mesh_terms: D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000145:classification* / Q000235:genetics*; D050903:Nicotinamide N-Methyltransferase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase
keywords:    MTHFR gene;    NNMT gene; A1298C polymorphism; C677T polymorphism; Conotruncal heart disease; rs694539 polymorphism