Association between genetic variants of reported candidate genes or regions and risk of cleft lip with or without cleft palate in the polish population.
BACKGROUND
Cleft lip with or without cleft palate (CL/P) is one of the most common craniofacial malformations, with a complex and multifactorial etiology. Because of the genetic heterogeneity of facial clefts, the aim of this study was to investigate the contribution of previously reported candidate genes and chromosomal loci to the risk of CL/P in the Polish population.


METHODS
We performed an analysis of 18 polymorphisms of FOXE1, IRF6, MSX1, PAX9, TBX10, FGF10, FGFR1, TGFalpha, TGFbeta3, SUMO1, and the chromosomal region 8q24 in a group of 175 patients with CL/P and a properly matched control group.


RESULTS
Highly significant results were observed for the IRF6 rs642961 variant and the 8q24 region's rs987525 (odds ratio [OR](AG+AAvsGG), 1.635; 95% confidence interval [CI], 1.153-2.319; p = 0.005; and OR(AC+AAvsCC), 1.962; 95% CI, 1.382-2.785; p = 1.4 x 10(-4), respectively). For rs987525, the results were also significant after correction for multiple comparisons. Borderline association with an increased risk of CL/P was also identified for the SUMO1 locus (rs2350350; OR(CGvsGG), 1.580; 95% CI, 1.056-2.363; p = 0.025).


CONCLUSIONS
Our findings confirmed that genetic variants of IRF6 and the polymorphism located in the 8q24 gene desert are strongly involved in the etiology of facial clefts in the Polish population sample.
Mostowska
Adrianna
A
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poland. amostowska@wp.pl
Hozyasz
Kamil K
KK
Wojcicki
Piotr
P
Biedziak
Barbara
B
Paradowska
Patrycja
P
Jagodzinski
Pawel P
PP
D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D025842:SUMO-1 Protein / Q000235:genetics
C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors; D025842:SUMO-1 Protein