title: MTHFR C677T and A1298C polymorphisms and risk of nonsyndromic orofacial clefts in a south Indian population.
abstract: OBJECTIVE
  Several lines of evidence suggest that the decrease in folate in periconceptional period or maternal use of folate antagonists has been associated with a higher risk of orofacial clefts (OFCs). MTHFR is a critical enzyme in folate metabolism that catalyzes the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, thus playing a vital role in DNA synthesis and DNA methylation. The aim of our study was to determine whether there is any association between the susceptibility to Nonsyndromic cleft lip with or without cleft palate (NSCL/P) amongst the variations of MTHFR genotypes in South Indian population.
  
  
  METHODS
  Our sample comprised 123 cases with NSCL/P and 141 controls without clefts or family history of clefting. The most common polymorphisms C677T (rs1801133) and A1298C (rs1801131) on the MTHFR gene were screened for the genotypes using PCR-RFLP.
  
  
  RESULTS
  Both C677T and A1298C are polymorphic with minor allele frequencies of 0.131 and 0.429, respectively, for controls. Genotype data in control and cleft groups are following the Hardy Weinberg Equilibrium. There were no significant differences in genotypes of both polymorphisms between controls and NSCL/P. The pairwise LD values (D' and r(2)) between C677T and A1298C are 1.0 and 0.096 respectively indicating no significant LD between these two SNPs. Haplotype phenotype analysis did not show the evidence for association. Gene-gene interaction showed the distribution of the observed combinations of the two MTHFR polymorphisms was not different between NSCL/P and controls (p=0.887).
  
  
  CONCLUSIONS
  Our results do not support the hypothesis, that variants in the MTHFR gene confer a risk for NSCL/P in the South Indian population.
authors.affiliation: Department of Plastic Surgery, Sri Ramachandra University, Chennai, India.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Murthy
authors.affiliation: Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India.
authors.forename: Venkatesh Babu
authors.initials: VB
authors.lastname: Gurramkonda
authors.affiliation: Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Karthik
authors.affiliation: Department of Biomedical Sciences, Sri Ramachandra University, Chennai, India. Electronic address: lvksbhaskar@gmail.com.
authors.forename: Bhaskar V K S
authors.initials: BV
authors.lastname: Lakkakula
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001921:Brain / Q000002:abnormalities*; D002648:Child; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Folate metabolism; MTHFR; Orofacial cleft; SNP