Family-based study of association between MAFB gene polymorphisms and NSCL/P among Western Han Chinese population.

BACKGROUND

Non-syndromic cleft lip with or without cleft palate (NSCL/P) are the most common human congenital birth defects with a complex etiology. MAFB has been reported as a candidate gene involved in the pathogenesis of NSCL/P from genome-wide association study (GWAS) findings, and no replication studies have been performed in Western Han Chinese.

OBJECTIVES

The aim of this study was to investigate the associations of MAFB among NSCL/P trios in Western Han Chinese.

MATERIAL AND

METHODS

We selected 6 single nucleotide polymorphisms (SNPs) (rs6072081, rs6065259, rs17820943, rs13041247, rs11698025 and rs6102085) near MAFB based on previous GWAS findings and recruited 298 case-parents trios with NSCL/P from Western Han Chinese population, while genotypes were done by SNPscan technology.

RESULTS

Strong evidence of an association was found at rs17820943 (p = 0.0023; odds ratio - ORtranmission = 0.7 and 95% confidence interval [CI]: 0.55-0.88) and rs13041247 (p = 0.0023; ORtranmission = 0.7 and 95% CI: 0.55-0.88) among NSCL/P; genotypic transmission-disequilibrium test (TDT) analysis further confirmed this. C/C homozygote at rs17820943 (z = 3.44 and p = 0.00058) and T/T homozygote at rs13041247 (z = 3.14 and p = 0.0017) was over-transmitted among NSCL/P, which indicated they could increase the risk of having an affected baby. Sliding window haplotype analysis showed that haplotypes consisting of C allele at rs17820943 and T allele at rs13041247 were still over-transmitted among NSCL/P (lowest p = 0.0021).

CONCLUSIONS

This study further confirmed that the targeted SNPs at MAFB were associated with NSCL/P trios from Western Han Chinese population, which provides more scientific evidence for the future research and genetic counseling.