[Association analysis between dystrophin gene polymorphism and non-syndromic cleft lip with or without cleft palate].

Abstract

Objectives: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect influenced by genetic and environmental factors, with genetic factors playing a major role. This study aims to investigate the association between the dystrophin (DMD) gene and NSCL/P in a Chinese Han population.

Methods: Four tag single nucleotide polymorphisms (SNPs) in the DMD gene were selected and allelic and genotype-based association analyses were performed on 1 780 patients with NSCL/P and 1 823 normal controls.

Results: Comparison with the controls showed that patients with NSCL/P presented three SNPs (rs5971698, rs5928208, and rs5972815) with significant associations with NSCL/P or its subphenotypes. Allelic association analysis revealed that rs5971698 was associated with NSCL/P, unilateral cleft lip with or without cleft palate (UCL/P), left cleft lip with or without cleft palate (LCL/P), unilateral cleft lip and cleft palate (UCLP), left cleft lip and cleft palate (LCLP), unilateral cleft lip (UCL), and left cleft lip only (LCL) (P<0.05); rs5928208 was associated with non-syndromic cleft lip and cleft palate (NSCLP), bilateral cleft lip with or without cleft palate (BCL/P), LCL/P, bilateral cleft lip and cleft palate (BCLP), and LCL (P<0.05); and rs5972815 was associated with UCLP, UCL, and right cleft lip only (RCL)(P<0.05), exhibiting significant laterality bias. Genotype analysis further confirmed these associations. Functional predictions suggested that different alleles at rs5928208 and rs5972815 may influence transcription factor binding affinity.

Conclusions: This study identified associations between SNPs in the DMD gene and NSCL/P in a Western Chinese Han population, providing new evidence for distinct genetic susceptibility loci among NSCL/P subtypes.