Polymorphic variants at 10q25.3 and 17q22 loci and the risk of non-syndromic cleft lip and palate in the Polish population.
BACKGROUND
Non-syndromic cleft lip and palate (CLP) is one of the most common birth defects. Recent genome-wide association studies (GWAS) have identified several novel risk loci associated with this craniofacial anomaly. Therefore, the objective of this report was to investigate the contribution of the top seven polymorphisms reaching genome-wide statistical significance in GWAS analyses in the Polish population.


RESULTS
Nucleotide variants located at chromosomal regions 1p22.1, 10q25.3, 17q22, and 20q12 were tested in a group of 206 patients with nonsyndromic CLP and a properly matched control group. Significant results, which persisted even after Bonferroni correction (p < 0.0071), were observed for polymorphisms located at 10q25.3 (rs7078160 and rs4752028) and 17q22 (rs227731). Under a recessive model, both rs7078160 and rs4752028 were associated with a greater than fourfold increase in the risk of CLP (odds ratio [OR] = 4.536; 95% confidence interval [CI], 1.678-12.265; p = 0.0012 and OR = 4.573; 95% CI, 1.817-11.512; p = 0.0004, respectively). Polymorphism rs227731 increased the risk of CLP when analyzed under a dominant model (OR = 1.732; 95% CI, 0.184-2.253; p = 0.0044). Borderline association was alsoidentified for the 1p22.1 locus (rs481931). Moreover, 10q25.3 haplotypes were significantly associated with a susceptibility to CLP.


CONCLUSIONS
Our evaluation study confirmed a substantial association of polymorphisms located at chromosomal regions 10q25.3 and 17q22 with nonsyndromic CLP in the Polish population.
Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland. amostowska@wp.pl
Adrianna
A
Mostowska
Kamil K
KK
Hozyasz
Karolina
K
Wojcicka
Barbara
B
Biedziak
Pawel P
PP
Jagodzinski
D002648:Child; D002675:Child, Preschool; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D011044:Poland / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide