Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Mesoamerican population: Evidence for IRF6 and variants at 8q24 and 10q25.
BACKGROUND
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common of all birth defects. NSCL/P has a multifactorial etiology that includes both genetic and environmental factors. The IRF6 gene and three further susceptibility loci at 8q24, 10q25, and 17q22, which were identified by a recent genome-wide association scan (GWAS), are confirmed genetic risk factors for NSCL/P in patients of European descent.


METHODS
A case-control association study was performed to investigate whether these four risk loci contribute to NSCL/P in a Mesoamerican population using four single nucleotide polymorphisms to represent IRF6 and the three novel susceptibility loci. A total of 149 NSCL/P patients and 303 controls of Mayan origin were included.


RESULTS
Single marker analysis revealed a significant association between NSCL/P and risk variants in IRF6 and the 8q24 and 10q25 loci. In contrast to previous findings, the association at the 8q24 locus was driven solely by homozygote carriers of the risk allele. This suggests that this locus might act in a recessive manner in the Mayan population. No evidence for association was found at the 17q22 locus. This may have been attributable to the limited power of the sample.


CONCLUSIONS
These results suggest that IRF6 and the 10q25 and 8q24 loci confer a risk for the development of NSCL/P in persons of Mayan origin.
Rojas-Martinez
Augusto
A
Department of Biochemistry and Molecular Medicine, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico.
Reutter
Heiko
H
Chacon-Camacho
Oscar
O
Leon-Cachon
Rafael B R
RB
Munoz-Jimenez
Sergio G
SG
Nowak
Stefanie
S
Becker
Jessica
J
Herberz
Ruth
R
Ludwig
Kerstin U
KU
Paredes-Zenteno
Mario
M
Arizpe-Cantú
Abelardo
A
Raeder
Susanne
S
Herms
Stefan
S
Ortiz-Lopez
Rocio
R
Knapp
Michael
M
Hoffmann
Per
P
Nöthen
Markus M
MM
Mangold
Elisabeth
E
D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D007197:Indians, Central American / Q000235:genetics*; D050835:Interferon Regulatory Factors / Q000235:genetics*; D012307:Risk Factors
C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors