Evaluation of the Role of Two SNPs in MTHFR Gene Polymorphisms (rs1801133) 677 C>T and (rs 1801131) 1298A>C with Homocysteine Level in Iraqi Patients with Chronic Kidney Disease

Abstract

Objectives: Objectives: The current study was designed to evaluate the role of MTHFR gene (rs1801133 and rs1801131) polymorphisms and investigate the serum Homocysteine level in Iraqi patients with CKD. Materials and Methods: Blood samples were collected from fifty CKD patients and fifty healthy control group aged (20 –65) years who attended Lmamain Al Kadhemain Medical Teaching Hospital and Al-Numan Hospital in Baghdad, Iraq. The genotyping study of the MTHFR gene at rs1801133 and rs1801131 was determined using HRM-PCR, and the serum level of Homocysteine was measured using ELISA kits. Results: Serum Hcy concentration was significantly (p˂0.01) increased in CKD patients compared to apparently healthy individuals (2.918Umol/L versus 1.621 Umol/L respectively). The frequencies and genotypes of alleles for the MTHFR gene at rs1801133 SNP in CKD patients versus healthy subjects revealed that the TT genotype percentage was in CKD patients significantly higher than in control groups (30% versus 14%, respectively). At the same time, the CT genotype was a considerably more significant percentage in CKD patients than in control groups (46% versus 16%, respectively). The frequency of the T allele was 53% and 22% for CKD patients and healthy individuals, respectively. In contrast, C allele frequency values were 47% and 78% for CKD patients and control groups, respectively. The frequencies of genotypes and alleles for the MTHFR gene at rs1801131 SNP showed that the percentage of CC genotype was in CKD patients significantly higher than that of control groups, 46% versus 12%, respectively, while C allele frequency values were 55% and 19% for CKD patients and control groups. Also, allele frequency values were 45% and 81% for CKD patients and healthy individuals, respectively. In this study, four haplotypes (AC, AT, CT, CC), certain variations in the MTHFR gene, specifically the CT haplotype formed by rs1801133 and rs1801131, have been related to an increased risk of chronic kidney disease. Conversely, the AC and AT haplotypes may have a protective effect against CKD, with the AC haplotype showing significant protection (OR, 0.45, 95% CI 0.06–0.5, p=0.0009). Conclusions: It was concluded from the current study that variants of the MTHFR gene have a role in the pathogenesis of CKD.

Keywords

• chronic kidney diseases
• mthfr gene
• snps
• polymorphism
• hrm
• homocysteine level
• elisa