Association between single-nucleotide polymorphisms on chromosome 1p22 and 20q12 and nonsyndromic cleft lip with or without cleft palate: new data in Han Chinese and meta-analysis.

ABSTRACT

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common congenital malformation associated with genetic and environmental risk factors. A recent genome-wide association study identified two novel susceptibility loci on chromosomes 1p22 and 20q12; however, conflicting results, especially for 1p22, have been reported in Han Chinese population. The aims of this study were to replicate this association with risk of NSCL/P in the southern Han Chinese population and to discern the effect of these loci by a meta-analysis. METHODS: To this end, 305 patients with NSCL/P, 356 phenotypically normal controls, and an additional 176 case-parent trios were recruited. Four of the previously associated single nucleotide polymorphisms (SNPs) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Furthermore, two published datasets were combined with the present results to determine the precise roles of the loci. RESULTS: SNPs (rs6072081, rs13041247, and rs6102085) on 20q12 were found to be strongly associated with NSCL/P (Bonferroni-corrected and χ(2) test; p values < 0.05). Subsequent analysis of the case-parent trio provided similar results. However, neither the association study nor the trio analysis supported a causative role for SNP rs560426 on 1p22 in NSCL/P susceptibility. Stratified meta- analysis combining Chinese samples supported our findings. CONCLUSIONS: This cross-validation study confirmed the previous findings that SNPs in 20q12 are associated with NSCL/P in Han Chinese population. We further conclude that rs560426 on 1p22 might not have a major influence on susceptibility to NSCL/P in southern Han Chinese, but future studies with other Han Chinese populations are needed.