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 677CT and 1298AC 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.
Description
Master
Keywords
Biological Science , Gene polymorphisms , Nonsyndromic orofacial clefts