Rafighdoost Houshang, Hashemi Mohammad, Asadi Hossein, Bahari Gholamreza
Department of Anatomy, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Congenit Anom (Kyoto). 2018 Jul;58(4):130-135. doi: 10.1111/cga.12271. Epub 2018 Feb 6.
Nonsyndromic cleft lip with or without cleft palate is a common congenital deformity worldwide with multifaceted etiology. Interaction of genes and environmental factors has been indicated to be related with susceptibility to nonsyndromic cleft lip with or without cleft palate. Some WNT genes which are involved in craniofacial embryogenesis may play a key role in the pathogenesis of nonsyndromic cleft lip with or without cleft palate. In the present study, we aimed to inspect the relationship between WNT3 (rs3809857 and rs9890413), WNT3A (rs752107 and rs3121310), and WNT10a rs201002930 (c.392 C>T) polymorphisms and nonsyndromic cleft lip with or without cleft palate in an Iranian population. The present case-control study was carried out on 120 unrelated nonsyndromic cleft lip with or without cleft palate patients and 112 healthy subjects. The variants were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. The findings suggest that the rs3809857 polymorphism significantly decreased the risk of nonsyndromic cleft lip with or without cleft palate in codominant (odds ratio = 0.16, 95% confidence interval = 0.03-0.75, P = 0.020, TT vs GG), recessive (odds ratio = 0.16, 95% confidence interval = 0.03-0.72, P = 0.009, TT vs GG + GT) inheritance models. The rs9890413 variant marginally decreased the risk of nonsyndromic cleft lip with or without cleft palate in codominant (odds ratio = 0.41, 95% confidence interval = 0.17-0.99, P = 0.047, AG vs AA) model. Regarding C392T variant, the findings revealed that this variant significantly decreased the risk of nonsyndromic cleft lip with or without cleft palate in codominant (odds ratio = 0.24, 95% confidence interval = 0.10-0.58, P = 0.002, CT vs CC) and allele (odds ratio = 0.26, 95% confidence interval = 0.11-0.62, P = 0.002, T vs C) models. No significant association was observed between the rs752107 and rs3121310 variants and risk/protection of nonsyndromic cleft lip with or without cleft palate. Stratified analysis showed that WNT10a rs201002930 (c.392 C>T) significantly decreased the risk of cleft lip with cleft palate and cleft palate only. In summary, the results suggest an association between WNT genes polymorphisms and the risk nonsyndromic cleft lip with or without cleft palate in a sample of the southeast Iranian population.
非综合征性唇裂伴或不伴腭裂是一种常见的先天性畸形，病因是多方面的。基因与环境因素的相互作用已被表明与非综合征性唇裂伴或不伴腭裂的易感性有关。一些参与颅面胚胎发育的WNT基因可能在非综合征性唇裂伴或不伴腭裂的发病机制中起关键作用。在本研究中，我们旨在探讨WNT3（rs3809857和rs9890413）、WNT3A（rs752107和rs3121310）以及WNT10a rs201002930（c.392 C>T）基因多态性与伊朗人群中非综合征性唇裂伴或不伴腭裂之间的关系。本病例对照研究对120例无关的非综合征性唇裂伴或不伴腭裂患者和112名健康受试者进行。通过聚合酶链反应-限制性片段长度多态性方法对变异进行基因分型。研究结果表明，rs3809857基因多态性在共显性（优势比=0.16，95%置信区间=0.03-0.75，P=0.020，TT与GG相比）、隐性（优势比=0.16，95%置信区间=0.03-0.72，P=0.009，TT与GG+GT相比）遗传模型中显著降低了非综合征性唇裂伴或不伴腭裂的风险。rs9890413变异在共显性（优势比=0.41，95%置信区间=0.17-0.99，P=0.047，AG与AA相比）模型中略微降低了非综合征性唇裂伴或不伴腭裂的风险。关于C392T变异，研究结果显示该变异在共显性（优势比=0.24，95%置信区间=0.10-0.58，P=0.002，CT与CC相比）和等位基因（优势比=0.26，95%置信区间=0.11-0.62，P=0.002，T与C相比）模型中显著降低了非综合征性唇裂伴或不伴腭裂的风险。未观察到rs752107和rs3121310变异与非综合征性唇裂伴或不伴腭裂的风险/保护之间存在显著关联。分层分析表明，WNT10a rs201002930（c.392 C>T）显著降低了唇裂伴腭裂和单纯腭裂的风险。总之，结果表明在伊朗东南部人群样本中，WNT基因多态性与非综合征性唇裂伴或不伴腭裂的风险之间存在关联。
