Chen Renji, Guo Siyuan, Wang Xin, Mu Yue, Duan Erling, Xu Yi
1 Department of Oral and Maxillofacial Plastic and Traumatic Surgery, Beijing Stomatological Hospital, Capital Medical University , Beijing, China .
2 Treatment Center of Cleft Lip and Palate, Beijing Smile Angel Children's Hospital , Beijing, China .
Genet Test Mol Biomarkers. 2018 Jul;22(7):420-424. doi: 10.1089/gtmb.2017.0252. Epub 2018 Jun 22.
Nonsyndromic cleft lip with or without palate (NSCL/P) represents a complex condition caused by genetic and environmental factors. The aim of this study was to investigate the relationship between the EPHA3 polymorphisms and NSCL/P.
To investigate the relationship between five EPHA3 single nucleotide polymorphisms (SNPs) and NSCL/P, we selected 180 affected patients and 167 normal controls from the Chinese Han Population. EPHA3 SNPs (rs7650466, rs1398197, rs17801309, rs1054750, and rs7632427) were genotyped using the SNaPshot technique; bioinformatic analyses were performed to determine if any of them were potentially functional SNPs.
The rs7650466 T allele was associated with the incidence of NSCL/P (OR, 0.211; 95% CI, 0.131-0.338; adjusted p = 4.881 × 10) and cleft lip with or without palate (CL/P) (OR, 0.176; 95% CI, 0.104-0.297; adjusted p = 3.617 × 10), as well as with protective and dominant effects in both conditions. The rs7650466 T allele could be associated with reduced risk of the malformation. In a bioinformatics analysis, we found potential matching sites (miR-1255a, miR-125a-3p, miR-143, and miR-552) for rs7650466 and preliminarily analyzed its potential function.
Collectively, our data suggest that the EPHA3 rs7650466 polymorphism confers genetic risk for NSCL/P in the Chinese Han Population. Furthermore, rs7650466 is associated with CL/P incidence in stratified analyses, but not with cleft palate only.
非综合征性唇腭裂（NSCL/P）是一种由遗传和环境因素引起的复杂病症。本研究的目的是调查EPHA3基因多态性与NSCL/P之间的关系。
为了研究5个EPHA3单核苷酸多态性（SNP）与NSCL/P之间的关系，我们从中国汉族人群中选取了180例患病患者和167例正常对照。使用SNaPshot技术对EPHA3 SNPs（rs7650466、rs1398197、rs17801309、rs1054750和rs7632427）进行基因分型；进行生物信息学分析以确定其中是否有潜在的功能性SNP。
rs7650466的T等位基因与NSCL/P的发病率相关（比值比，0.211；95%置信区间，0.131 - 0.338；校正p = 4.881×10）以及与伴或不伴腭裂的唇裂（CL/P）相关（比值比，0.176；95%置信区间，0.104 - 0.297；校正p = 3.617×10），并且在这两种情况下都具有保护和显性效应。rs7650466的T等位基因可能与畸形风险降低相关。在生物信息学分析中，我们发现了rs7650466的潜在匹配位点（miR - 1255a、miR - 125a - 3p、miR - 143和miR - 552）并初步分析了其潜在功能。
总体而言，我们的数据表明EPHA3 rs7650466基因多态性在中国汉族人群中赋予了NSCL/P的遗传风险。此外，在分层分析中rs7650466与CL/P发病率相关，但与仅腭裂无关。
