Single-nucleotide polymorphisms of methylenetetrahydrofolate reductase gene in a South Indian cohort with nonsyndromic cleft lip with or without palate

摘要

Objective: Clefts of the lip, with or without cleft palate and cleft palate only, collectively called as orofacial clefts (OFCs) are one of the most common congenital malformations with varying degrees of penetrance and phenotype expressions. The aim of this study was to investigate the association between methylenetetrahydrofolate reductase (MTHFR) cytosine-to-thymine (c. 677 CT), adenine-to-cytosine (c.1298 AC) single- nucleotide polymorphisms (SNPs) and South Indian patients with the nonsyndromic cleft lip with or without palate (NSCL ± P). Methods: A cohort consisting of 25 cases of NSCL ± P and 18 controls from a South Indian cohort were included in this case–control study. Genetic analysis of c.677CT and c.1298A C polymorphisms in the MTHFR gene was carried out using Sanger sequencing and analyzed from chromatogram profiles. Data interpretation was done using statistical software MedCalc Statistical Software version 16.2 and the Statistical Package for the Social Sciences (SPSS version 22.0). Results: DNA sequence analysis of the MTHFR gene revealed c. 677CT and c. 1298AC polymorphisms in 16% and 76% of NSCL ± P cases, respectively. Heterozygous variant in MTHFR c. 1298AC polymorphism was found to be a significant risk factor (P = 0.0164) for NSCL ± P in South Indian ethnic population. c.677CT polymorphism, in particular, was apparently dormant overall in the study population. These results offer certain novelty in terms of the distinctive pattern in SNPs of genotypes observed in the study. Conclusion: NSCL ± P is one of the most common and challenging congenital malformations with complex etiological basis. Common risk factors such as MTHFR SNPs, namely c.677CT and c.1298AC, are subjected to variations in terms of ethnic group, geographic region and micro/macro-environmental factors. Overall, our study has explored part of South Indian ethnic population and revealed a different and unique distribution of mutations in this sample population.