A study of mthfr gene polymorphisms in patients with nonsyndromic orofacial clefts and their parents

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Date
2009
Authors
Pal, Sumita
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Abstract
This thesis describes the association of two important MTHFR gene single nucleotide polymorphisms 677CT and 1298AC with orofacial clefts in the Malay population. Two study methods, Case control and Transmission disequilibrium test (TDT) were employed. The subjects included 53 Malay patients with orofacial clefts, 53 mothers, 49 fathers and 49 controls for the case control study. Thirty eight complete triads of mother-father-child were studied for transmission of variant alleles from parents to offspring by using TDT. The genotyping was done by Polymerase Chain Reaction (PCR) followed by restriction fragment length polymorphism (RFLP) and gel electrophoresis. The frequency of MTHFR SNP 677CT in the control group was found to be lower (14.3%) than that in Caucasian general populations (30% in some studies). However, the prevalence of 1298AC in the control group (28.5%) was similar to that of other populations (27-36%). The prevalence of MTHFR 677 heterozygous CT genotype in the maternal population (n=53), was found to be lower (5.6%) compared to that in controls without orofacial clefts (14.3%) but the difference was not statistically significant (P=0.340). The TDT did not show a significantly low transmission of T allele from mothers to offspring either (P=0.38), but the risk of transmitting the T allele from mothers carrying this allele was lower compared to that of the wild type C allele (OR=0.59, 95% CI=0.187-1.921). This indicated a possible protective role of maternal T allele in orofacial clefts in the present study. No association was found between MTHFR 677CT genotypes of child or father with orofacial clefts. No association was seen between MTHFR 1298AC genotypes of any group (mother, father or child) with the risk of orofacial clefts. Analysis of the four haplotypes (677C/1298A, 677C/1298C, 677T/1298A, 677T/1298C) derived from compound genotypes, showed an asymmetric distribution of haplotypes indicating linkage disequilibrium between these 2 loci (MTHFR 677CT and 1298AC), consistent with previous study findings. The test of transmission, TDT showed a significantly low transmission of haplotype 677T/1298A from parents to offspring (P=0.018) indicating an inverse association of this haplotype with orofacial clefts. The average serum folate was high in the study group mothers as well as in control mothers. A history of multivitamin containing folate intake during pregnancy was found in 83% of mothers. These findings ruled out the possibility of low maternal folate status as a risk factor for orofacial clefts. Larger studies in the Malay population are needed to confirm the present findings.
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Master
Keywords
Biological Science , Gene polymorphisms , Nonsyndromic orofacial clefts
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