Association of two variants C677T and A1298C MTHFR gene polymorphisms with ischemic heart, ischemic stroke and venous thromboembolism diseases in a sample of Arabic Iraqi patients

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Mustafa Ihssan Abbas Al-Mahroos
Bahir Abdul Razzaq Mshimesh
Mahmmod Riyadh Alhaleem


MTHFR gene polymorphism, two variants (C677T and A1298C), independent risk factor


Background: There are genetic polymorphisms mostly single amino acid substitution occurred in the MTHFR gene, mutant type of this gene inhibit the production of MTHFR enzyme, it may result in excess homocysteine level in plasma which is thought to be the susceptibility of occlusive vascular diseases. About 109 mutations in MTHFR have been described as causing severe MTHFR deficiency. The most common MTHFR gene polymorphism can be detected as two variants; C677T and A1298C single nucleotide polymorphism (SNP) that are relatively common in many populations worldwide.
Objective: For investigation of the association of two variants C677T and A1298C MTHFR gene polymorphisms with Ischemic heart, ischemic stroke and venous thromboembolism diseases.
Subjects and method: This study was a prospective case-control trial included 58 Arabic Iraqi patients (43 males and 15 females) aged between 20-64 years suffered from different cardiovascular and thromboembolic disorders. Whereas, control group included 52 subjects composed of 41 males and 11 females without any thrombotic event history. The detection of MTHFR genetic polymorphism (wild, heterozygous, homozygous) by using real time polymerase chain reaction technique (quantitative real time PCR) for two specific variants of MTHFR (C677T and A1298C) as single nucleotide polymorphism to assess allele frequency or genotype distribution
(CC,TT,CT and AA,CC, AC respectively).

Result: The wild type of A1298C MTHFR gene (AA) in patients group was 37.93% versus 59.62% in control group with no significant difference (p=0.054). The frequency of the heterozygous genotype (AC) was higher in patients group (39.66%) than control group (30.77%) with a signficant difference (OR= 3.66, 95%CI= 1.14-11.77, p =0.027). This association seems to be in recessive model as the frequency of AC+CC in patients was 62.07% compared with 40.38% in controls (OR= 2.42, 95% CI= 1.12-5.2, p= 0.024). The mutant homozygous genotype (CC) was slightly more frequent among patients group than control group (22.41% vs. 9.61%) with no significant difference. At allelic level, the frequency of C allele in patients group was higher than those with control group (42.24% vs. 25%) with a highly significant difference (OR= 2.19, 95%CI= 1.23-3.91, p= 0.008).
Conclusion: Interestingly, patients those had carried heterozygous MTHFR A1298C genotype AC were 3.5 fold risk of exposure to ischemic heart disease, ischemic stroke and venous thromboembolism when compare with those carrying wild AA genotyping of the same SNP. Multivariate analysis between patients group and control group in the presence of A1298C MTHFR gene polymorphism appears that heterozygous MTHFR A1298C genotype AC is considered as independent risk factor for association of ischemic heart disease, ischemic stroke and venous thromboembolism. 

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