Association Between DLX4 Polymorphisms and Nonsyndromic Orofacial Clefts in a Chinese Han Population. (March 2019)

• Record Type: Journal Article
• Authors: He, Miao; Bian, Zhuan
• Is Part Of: Cleft palate-craniofacial journal. Volume 56:Number 3(2019)
• Page Start: 357
• Page End: 362
• Publication Date: 2019-03
• Subjects: orofacial cleft -- association study -- DLX4 -- SNP -- haplotype -- susceptibility; Cleft palate -- Periodicals; Skull -- Abnormalities -- Periodicals; Cranial manipulation -- Periodicals; Skull -- Abnormalities -- Surgery -- Periodicals; Face -- Abnormalities -- Surgery -- Periodicals; Fente palatine -- Périodiques; Crâne -- Malformations -- Périodiques; Manipulation crânienne -- Périodiques; Crâne -- Malformations -- Chirurgie -- Périodiques; Face -- Malformations -- Chirurgie -- Périodiques; Cleft palate; Cranial manipulation; Face -- Abnormalities -- Surgery; Skull -- Abnormalities; Skull -- Abnormalities -- Surgery; Cleft Lip; Cleft Palate; Facial Bones -- abnormalities; Skull -- abnormalities; Periodicals; Periodicals; Periodicals; 617.522
• DOI: 10.1177/1055665618775723
• Languages: English
• ISSNs: 1055-6656

Abstract

Objective: Distal-less 4 ( DLX4 ) was recently identified as the causative gene for a syndromic form of cleft lip with or without cleft palate, and further biological analyses have established the importance of Dlx4 gene in craniofacial development, which suggested DLX4 as a promising candidate to further investigate any possible association between DLX4 polymorphisms and risk to nonsyndromic orofacial clefts (NSOFCs). Design: Single-nucleotide polymorphisms (SNPs) with minor allele frequency >5% in the Han Chinese population which locate in the 5′ flanking region, 5′/3′-untranslated region, or coding region with nonsynonymous changes in DLX4 were selected. Four SNPs (rs58769681, rs1058562, rs1058564, and rs8066341) were thus included in the following genotyping using the TaqMan 5′-exonuclease allelic discrimination assay in a case–control cohort with 1522 individuals. Results: None of SNPs were associated with NSOFCat the allele and genotype levels in general and stratified single-marker analysis, including genotypic distributions under different modes of inheritance. In linkage disequilibrium (LD) analysis, we found strong LD ( r 2 > 0.8) between any 2 of the SNPs, respectively. Further haplotyping identified haplotypes C-C (formed by rs1058564 and rs1058562) and C-C-A (formed by rs1058564, rs1058562, and rs58769681) which reached the significance threshold ( P < .05); nevertheless, none of them survived the multiple comparison correction. Conclusions: Our findings indicated the hypothesis that DLX4 variants contributing to NSOFC risk should be interpreted with caution. Further replications in diverse ethnic origins and larger cohorts are still warranted.