Cleft Lip and Palate in Vietnam and Folate-related Genes
Poster Number
18
Introduction/Abstract
The etiology of nonsyndromic cleft lip with or without cleft palate (NCLP) is multifactorial, including genetic and environmental factors. Folate-related genes methylenetetrahydrofolate reductase (MTHFR) and reduced folate carrier 1 (RFC1) are among those genetic factors most intensively studied. When their function is altered due to mutations, a decreased utilization of folate slows down cell multiplication and it may contribute to orofacial clefting. RFC1 (Reduced Folate Carrier 1) gene that encodes a cell membrane protein essential for internalizing folate bound to a folate-binding protein from circulating blood into cells.
Purpose
Purpose of our study was to determine whether MTHFR677CT and the RFC180AG polymorphisms are associated with NCLP in CanTho, Vietnam.
Method
A case-control study design was used. Cases (individuals affected with NCL/P; n=38) and controls (n=33) for this study were identified during Rotaplast medical mission to CanTho, Vietnam. Diagnosis of NCL/P was determined by medical geneticist (MMT) conducting physical examination of each individual. Controls (n = 33) were recruited in the same hospital. Venous blood and saliva was obtained for DNA analysis. DNA was isolated from dry blood or saliva spots. MTHFR 677CT and RFC1 80AG genotypes were established by PCR amplification and single nucleotide conformational polymorphism detection using polyacrylamide gel electrophoresis (PAGE).
Results
Mutations of the MTHFR 677th nucleotide were relatively rare in CanTho samples of cases and controls that we studied. We found a different proportion of genotypes in cases and controls for MTHFR 677CT, but only one homozygote TT (in controls). There were twice as many CT heterozygotes in cases compared to controls (34.2% vs 15.2%) and thus a higher T allele frequency in cases (0.171) compared to controls (0.106) was found. However, these differences were not significant. Very interesting findings were revealed by analysis of RFC1 80AG. Mutated allele G was common in cases as well as in controls (higher in cases - 0.554 compared to controls - 0.5). Although GG genotypes were observed in the same proportions in cases and in controls (27 % vs 27.3%), lower proportion of AA homozygotes (16.2% vs 27.3%) and higher proportion of AG heterozygotes (56.8% vs 45.4%) were observed. The difference in distribution of genotypes between cases and controls was statistically significant (p=0.041).
Significance
The present study suggests association of 80AT variant of the RFC1 gene with NCL/P in CanTho Vietnam. No association was observed for 677CT variant of MTHFR . The study continues by increasing size of samples for cases and controls and by involving also mothers and fathers of cases.
Location
DeRosa University Center, Stockton campus, University of the Pacific
Format
Poster Presentation
Cleft Lip and Palate in Vietnam and Folate-related Genes
DeRosa University Center, Stockton campus, University of the Pacific
The etiology of nonsyndromic cleft lip with or without cleft palate (NCLP) is multifactorial, including genetic and environmental factors. Folate-related genes methylenetetrahydrofolate reductase (MTHFR) and reduced folate carrier 1 (RFC1) are among those genetic factors most intensively studied. When their function is altered due to mutations, a decreased utilization of folate slows down cell multiplication and it may contribute to orofacial clefting. RFC1 (Reduced Folate Carrier 1) gene that encodes a cell membrane protein essential for internalizing folate bound to a folate-binding protein from circulating blood into cells.
