Methylene-Tetrahydrofolate Reductase Gene C677T and A1298C Polymorphisms as a Risk Factor for Crimean-Congo Hemorrhagic Fever

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is a deadly viral disease. Methylene-tetrahydrofolate reductase (MTHFR) has an important role in folate metabolism, and also in the formation of new cells, DNA synthesis, repair and methylation. We aimed to examine the relationship between MTHFR gene C677T (Ala222Val, rs1801133) and A1298C (Glu429Ala, rs1801131) polymorphisms with CCHF in a Turkish population. Totally 273 participants were included in the current study. One hundred forty-one participants were CCHF patients and one hundred thirty-two participants were healthy controls. The polymerase chain reaction (PCR) and further restriction fragment length polymorphism (RFLP) assays were applied to determine the genotypes of MTHFR polymorphisms. We did not find any differences between the CCHF patients and healthy controls in terms of allele and genotype distributions of both the C677T and A1298C polymorphisms. After dividing the CCHF patients into different groups, we found that AC and AC + CC genotype frequencies of A1298C polymorphism were higher in Non-fatal patients compared to controls (p = 0.014 and p = 0.027, respectively). In composite genotype analysis between different groups, the frequency of CT-AA composite genotype, which is formed by C677T-A1298C polymorphisms, was found to be significantly higher in Mild CCHF patients compared to both Severe CCHF patients and controls (p = 0.036 and p = 0.008, respectively). In conclusion, in this study, we found a relationship between CCHF and MTHFR gene polymorphisms. Genotypes consisting C allele of A1298C polymorphism poses a risk for CCHF in Non-fatal group and CT-AA composite genotype of MTHFR gene C677T and A1298C polymorphisms showed a predisposition to Mild CCHF.