Genetic polymorphisms (MTHFR,RFC1,MSX1) and orofacial clefts in different populations
Both genetic and environmental factors are involved in etiology of nonsyndromic cleft lip and palate (NCLP). Associations of nucleotide polymorphisms of several “candidate” genes (TGFA, TGFB3, MTHFR, RFC1, MSX1, IRF6, PVRL1) with NCLP were shown. Approximately 15-20% of NCLP are determined by combinations of four susceptibility genes: MSX1, RFC1, IRF6 and TGFB3.
OBJECTIVES: We studied the C677T polymorphism of the MTHFR gene, the A80G polymorphism of the RFC1 gene, and the CA-repeat polymorphism in the MSX1 gene among individuals with NCLP and among unaffected controls in nine locations.
METHODS: Altogether 619 cases and 468 controls were identified during Rotaplast medical missions to different locations in Argentina (2), Chile (2), Guatemala (1), India (1), Philippines (1), and Venezuela (2). The MTHFR and RFC1 genotypes were established using PCR amplification followed by PAGE. Sequencing was used for determination of the MSX1 genotypes.
RESULTS: The highest G allele frequency of the RFC1 A80G polymorphism was found among cases in Guatemala. When compared to controls, the difference was statistically significant (p=0.016). The G allele frequency among cases was higher in all locations, but the difference from controls was not always statistically significant. Regarding the MTHFR C677T polymorphism, the highest statistically significant difference between cases and controls in the T allele frequency (p=0.031) was found in Guatemala. In the majority of the studied locations, the MSX1 A4A4 genotype (homozygote for 9 CA repeats) was most common in both cases and controls. However, in some locations, the difference between cases and controls was statistically significant.
CONCLUSIONS: It is suggested that a different spectrum of genetic factors constituting a genetic susceptibility to NCLP exists in different populations. The study is continued with the aim to increase a sample size and a significance of the results.
This study was supported by Rotaplast International Inc.
Division: IADR General Session
Meeting:2006 IADR General Session (Brisbane, Australia) Location: Brisbane, Australia
Year: 2006 Final Presentation ID:491 Abstract Category|Abstract Category(s):Craniofacial Biology
Authors
Tolarova, Marie
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)
Fallah, Basma
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)
Porter, Micah
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)
Dalbah, Lana
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)
Tolar, Miroslav
( University of California - San Francisco, San Francisco, CA, USA
)
Pawar, Tripti
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)
Obara, Midori
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)
Al-jabeiti, Alia
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)
Handelin, Mark
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)
Costanzo, Cory
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)
Oh, Heesoo
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)
Salahuddin, Reem
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)
Wu, Jamson
( University of the Pacific School of Dentistry, San Francisco, CA, USA
)