Abstract
BACKGROUND: Non-syndromic cleft lip with/without cleft palate (NSCL/P) is a common congenital condition with a complex aetiology reflecting multiple genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in ABCA4 have been associated with NSCL/P in several studies, although there are some inconsistent results. This study aimed to evaluate whether two SNPs in ABCA4, namely rs4147811 and rs560426, are associated with NSCL/P occurrence in the Polish population. METHODS: The study included 627 participants: 209 paediatric patients with NSCL/P and 418 healthy newborn controls. DNA was isolated from the saliva of NSCL/P patients and from umbilical cord blood in the controls. Genotyping of rs4147811 and rs560426 was performed using quantitative PCR. RESULTS: The rs4147811 (AG genotype) SNP in ABCA4 was associated with a decreased risk of NSCL/P (odds ratio (OR) 0.57; 95% confidence interval (CI) 0.39-0.84; p = 0.004), whereas the rs560426 (GG genotype) SNP was associated with an increased risk of NSCL/P (OR 2.13; 95% CI 1.31-3.48; p = 0.002). LIMITATIONS: This study-based on the correlation between single genetic variants and the occurrence of different phenotypes-might have limited power in detecting relevant, complex inheritance patterns. ORs are often low to moderate when investigating the association of single genes with the risk of a complex trait. Another limitation was the small number of available NSCL/P samples. CONCLUSIONS: The results suggest that genetic variations in ABCA4 are important risk markers of NSCL/P in the Polish population. Further investigation in a larger study group is warranted.