ASSOCIATION OF REDUCED FOLATE CARRIER ONE GENE 80AG POLYMORPHISM WITH NONSYNDROMIC CLEFT LIP AND PALATE
Introduction/Abstract
Mutations in folate pathway genes have been shown to be associated with several birth defects including neural tube defects, conotruncal heart defects, and nonsyndromic cleft lip and palate (NCLP). For the last decade, we studied polymorphisms of those genes in cleft populations. The Reduced Folate Carrier One gene (RFC1, also known as SLC19A1) encodes for a cellular surface transmembrane protein that provides transport of folate from diet through the cell membrane. Several single nucleotide polymorphisms (SNP) of the RFC1 gene exist and one common SNP in the RFC1 gene – 80AG has been studied in NCLP populations.
Purpose
To study association of RFC1 80AG polymorphism with NCLP in ethnically diverse populations and discuss the results with our previous findings and findings of others.
Method
A case control study design was used. During the past 12 months, three datasets of cases (individuals affected with NCLP) and controls (unaffected individuals with no history of clefts or other birth defects in the family from the same location) from Egypt, India and Venezuela were analyzed - altogether, 245 cases (Sohag, Egypt 116; Udaipur, India 57; Cumana, Venezuela 72) and 168 controls (Sohag, Egypt 81; Udaipur, India, 30; Cumana, Venezuela 57). Venous blood or saliva was collected from cases and controls during Rotaplast medical missions. Specimens were spotted on filter paper, allowed to dry, and transported to the Pacific Craniofacial Genetics Laboratory where DNA analyses were performed using laboratory protocol [DNA isolation, PCR, agarose gel electrophoresis for confirmation of both sufficient amplification and absence of contamination, PAGE (polyacrylamide gel electrophoresis) for genotype analysis].
Results
Statistically significant differences between cases and controls were found in Sohag samples for genotype distribution (p=0.039) and also for allele frequencies (p=0.009). Samples from two other locations (Udaipur and Cumana) showed statistical difference neither in genotype distributions nor in allele frequencies.
Significance
When compared with our previous studies on RFC1 80AG polymorphism associated with NCLP, the Egyptian results support our findings in populations studied in Argentina and Central America. One (Nagamangala) of two other Indian populations showed association. Two Venezuelan populations that we have previously studied showed associations. In summary, our research results reflect a genetic diversity of different populations in the world. It seems that the same anomaly can be caused by different genetic and environmental factors.
Location
DeRosa University Center, Stockton campus, University of the Pacific
Format
Poster Presentation
ASSOCIATION OF REDUCED FOLATE CARRIER ONE GENE 80AG POLYMORPHISM WITH NONSYNDROMIC CLEFT LIP AND PALATE
DeRosa University Center, Stockton campus, University of the Pacific
Mutations in folate pathway genes have been shown to be associated with several birth defects including neural tube defects, conotruncal heart defects, and nonsyndromic cleft lip and palate (NCLP). For the last decade, we studied polymorphisms of those genes in cleft populations. The Reduced Folate Carrier One gene (RFC1, also known as SLC19A1) encodes for a cellular surface transmembrane protein that provides transport of folate from diet through the cell membrane. Several single nucleotide polymorphisms (SNP) of the RFC1 gene exist and one common SNP in the RFC1 gene – 80AG has been studied in NCLP populations.
