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Background <p>Congenital heart diseases (CHDs) represent the most common congenital malformations, with genetic factors playing a crucial role in their pathogenesis. Genes involved in folate, homocystein, and methionine metabolism have been implicated in CHD susceptibility. Methionine synthase reductase (MTRR<i>)</i> is a key regulatory enzyme intricately linked to the homocystein metabolic pathway. This study aimed to investigate the association of <i>MTRR</i> single nucleotide polymorphisms (SNPs) (A66G and C524T) with non-syndromic acyanotic congenital heart disease (ACHD) in Egyptian children.</p> Methods <p>In this case–control study, we assessed the association between <i>MTRR</i> gene SNPs (A66G and C524T) and the risk of non-syndromic CHD in 120 children diagnosed with CHD and 180 healthy controls. Genotypic analysis was performed using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP).</p> Results <p>Analysis of the A66G polymorphism revealed significant differences in the frequency of the 66GG genotype between CHD cases and controls. The mutant G allele of A66G was significantly associated with ACHD (<i>P</i> &lt; 0.001). Similarly, the C524T polymorphism exhibited significant variation in genotype frequencies, with the homozygous 524TT and heterozygous 524CT genotypes being more prevalent among CHD patients compared to controls. The mutant T allele of C524T was strongly associated with ACHD (<i>P</i> &lt; 0.001). Furthermore, combined genotype analysis indicated a significantly increased risk of ACHD in individuals with AG/CT (<i>P</i> = 0.027), GG/CT (<i>P</i> = 0.002), AA/TT (<i>P</i> = 0.021), AG/TT (<i>P</i> = 0.007), and GG/TT (<i>P</i> &lt; 0.001) genotypic combinations. Regarding phenotypic correlations, the heterozygous AG genotype of A66G was significantly associated with atrial septal defects (ASD), whereas the homozygous GG genotype was linked to ventricular septal defects (VSD), ASD, and pulmonary stenosis (PS). For the C524T polymorphism, the heterozygous CT genotype was correlated with patent ductus arteriosus (PDA), while the homozygous TT genotype was associated with VSD, ASD, and PDA.</p> Conclusion <p>The findings suggest that <i>MTRR</i> (A66G and C524T) gene polymorphisms are associated with an increased risk of non-syndromic ACHD in Egyptian children. Additionally, specific polymorphic variants may predispose individuals to distinct acyanotic congenital heart diseases.</p>

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MTRR gene polymorphisms among Egyptian children with acyanotic congenital heart diseases: a case–control study

  • 期刊论文

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  • 发表日期：

    2025年7月11日

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  • Basma M. Shehata,
  • Iman Mohamed Abdel-Rahim Aly,
  • Nevin Tawfik Abed,
  • Shuzan Ali Mohamed,
  • Medhat Mohamed Helmy Hamed,
  • Nanies M. S. Soliman

摘要

Background

Congenital heart diseases (CHDs) represent the most common congenital malformations, with genetic factors playing a crucial role in their pathogenesis. Genes involved in folate, homocystein, and methionine metabolism have been implicated in CHD susceptibility. Methionine synthase reductase (MTRR) is a key regulatory enzyme intricately linked to the homocystein metabolic pathway. This study aimed to investigate the association of MTRR single nucleotide polymorphisms (SNPs) (A66G and C524T) with non-syndromic acyanotic congenital heart disease (ACHD) in Egyptian children.

Methods

In this case–control study, we assessed the association between MTRR gene SNPs (A66G and C524T) and the risk of non-syndromic CHD in 120 children diagnosed with CHD and 180 healthy controls. Genotypic analysis was performed using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP).

Results

Analysis of the A66G polymorphism revealed significant differences in the frequency of the 66GG genotype between CHD cases and controls. The mutant G allele of A66G was significantly associated with ACHD (P < 0.001). Similarly, the C524T polymorphism exhibited significant variation in genotype frequencies, with the homozygous 524TT and heterozygous 524CT genotypes being more prevalent among CHD patients compared to controls. The mutant T allele of C524T was strongly associated with ACHD (P < 0.001). Furthermore, combined genotype analysis indicated a significantly increased risk of ACHD in individuals with AG/CT (P = 0.027), GG/CT (P = 0.002), AA/TT (P = 0.021), AG/TT (P = 0.007), and GG/TT (P < 0.001) genotypic combinations. Regarding phenotypic correlations, the heterozygous AG genotype of A66G was significantly associated with atrial septal defects (ASD), whereas the homozygous GG genotype was linked to ventricular septal defects (VSD), ASD, and pulmonary stenosis (PS). For the C524T polymorphism, the heterozygous CT genotype was correlated with patent ductus arteriosus (PDA), while the homozygous TT genotype was associated with VSD, ASD, and PDA.

Conclusion

The findings suggest that MTRR (A66G and C524T) gene polymorphisms are associated with an increased risk of non-syndromic ACHD in Egyptian children. Additionally, specific polymorphic variants may predispose individuals to distinct acyanotic congenital heart diseases.