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. 2017 Spring;8(2):83-90.
doi: 10.22088/cjim.8.2.83.

Are polymorphisms in MTRR A66G and MTHFR C677T genes associated with congenital heart diseases in Iranian population?

Noormohammad Noori  1 , Ebrahim Miri-Moghaddam  2   3 , Asieh Dejkam  1 , Yasman Garmie  4 , Ali Bazi  5
Affiliations

Are polymorphisms in MTRR A66G and MTHFR C677T genes associated with congenital heart diseases in Iranian population?

Noormohammad Noori et al. Caspian J Intern Med. 2017 Spring.

Abstract

Background: The 5, 10-methyleneterahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are two essential enzymes involved in folate metabolism. The relationship between genetic polymorphisms and congenital heart defects (CHDs) is inconsistent. Our aim was to investigate the association between two well-known polymorphisms of MTHFR and MTRR genes, C677T and A66G, respectively, and CHDs in Iranian patients.

Methods: We enrolled 74 patients with ventricular septal defect (VSD) and 79 with tetralogy of fallot (TOF) along with 147 healthy controls. C677T and A66G polymorphisms were detected using tetra-primer ARMS (amplification refractory mutation system) PCR.

Results: Individuals carrying homozygote mutant (TT) genotype of C677T polymorphism represented the highest risk for CHDs (OR=7.3, 95% CI: 0.8-61, P=0.06). Also, significantly increased risk of VSD was observed in individuals with TT genotype (OR=10, 95% CI: 1-92.2, P=0.04). However, the frequency for variant allele (T) of C677T polymorphism was not statistically different between cases and controls (16.3% and 20.9%, respectively). For A66G polymorphism, we found that AG and GG genotypes had higher frequencies in the patients (48.4% and 21.6% respectively) than controls (42.9% and 15.6%, respectively). In line with this, combined AG+GG genotype represented with significantly elevated risk of CHDs (OR=1.6; 95% CI: 1-2.6, P=0.03). AG+GG combination was also identified as a risk factor for TOF (OR=1.8, 95% CI: 1-3.3, P=0.04).

Conclusion: We demonstrated that C677T polymorphism of MTHFR gene was significantly associated with VSD in our patients. Our study also suggested that A66G polymorphism of MTRR gene may contribute to the development of TOF in Iranians.

Keywords: 10-methyleneterahydrofolate reductase (MTHFR); 5; Methionine synthase reductase (MTRR); Tetralogy of fallot (TOF); Ventricular septal defect (VSD); congenital heart defects (CHDs).

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Frequencies of genotypes and alleles of A66G polymorphism of MTRR gene in the controls and the patients with CHDs. Figure indicates percentages of each genotype and allele in total population of the patients, as well as in separate subgroups of the patients with VSD and TOF
Figure 2
Figure 2
Frequencies of genotypes and alleles of C677T polymorphism of MTHFR gene among patients with two common types of CHDs (VSD and TOF), and its comparison with control group
See this image and copyright information in PMC

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