Investigating SPRY2 Single-Nucleotide Polymorphisms in the Etiology of Nonsyndromic Orofacial Cleft in the Chinese Han Population

Objective This study aimed to explore the relationship between the SPRY2 gene and nonsyndromic orofacial cleft (NSOC) in the Chinese Han population. Design A case–control study was conducted with a large cohort to analyze genetic associations. Setting The study was conducted in China, focusing on the Chinese Han ethnic group. Patients, Participants The study included 2494 Chinese Han patients with NSOC and 2255 healthy control individuals. Interventions Nine single-nucleotide polymorphisms (SNPs) of the SPRY2 gene were selected for association analysis, utilizing PLINK and Haploview software. Functional annotations were conducted using HaploReg, Encode, and 3D SNP prediction tools. Main Outcome Measure(s) The primary outcome measures were the associations of the selected SNPs with different types of NSOC, including nonsyndromic cleft lip with palate (NSCLP), nonsyndromic cleft lip with/without palate (NSCL/P), and nonsyndromic cleft palate only (NSCPO). Results Allelic association analysis revealed that allele T of rs700397 significantly increased the risk of NSCLP ( P = .00050, odds ratio [OR] = 1.49, 95% confidence interval [CI]: 1.19-1.85) and NSCL/P ( P = .0018, OR = 1.27, 95% CI: 1.09-1.47). Additionally, allele G of rs116994696 was associated with NSCPO ( P = .00024, OR = 1.67, 95% CI: 1.27-2.17). Four haplotypes demonstrated a significant association with NSCPO after Bonferroni correction. Conclusions The findings suggest that SNP rs700397 in the SPRY2 enhancer is associated with NSCLP and NSCL/P, while rs116994696 in the promoter is linked to NSCPO. This indicates that susceptibility SNPs in different regulatory elements may play a role in gene regulation related to NSOC.