Association of single nucleotide polymorphisms in AXIN2, BMP4, and IRF6 with Non-Syndromic Cleft Lip with or without Cleft Palate in a sample of the southeast Iranian population

Abstract Non-syndromic cleft lip with or without palate (NSCL/P) is a common congenital malformation worldwide, with complex etiology. It has been proposed that interaction of genes and environmental factors play a role in the predisposition to this disease. Objectives: The aim of this study was to examine the association between AXIN2 (axis inhibition protein 2) rs7224837, BMP4 (bone morphogenetic protein 4) rs17563, and IRF6 (interferon regulatory factor 6) rs861019 and 2235371 polymorphisms and NSCL/P in an Iranian population. Material and Methods: This case-control study was carried out on 132 unrelated NSCL/P patients and 156 healthy subjects. The variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The findings suggest that BMP4 rs17563 polymorphism significantly decreased the risk of NSCL/P in codominant (OR=0.36, 95%CI=0.17-0.79, p=0.012, CT vs CC and OR=0.11, 95%CI=0.01-0.88, p = 0.019, TT vs CC), dominant (OR=0.30, 95%CI=0.15-0.62, p = 0.0007, CT+TT vs CC), recessive (OR=0.12, 95%CI=0.02-0.99, p = 0.023, TT vs CC+CT), overdominant (OR=0.39, 95%CI = 0.18-0.84, p=0.021, CT vs CC+TT), and allele (OR=0.28, 95%CI=0.15-0.55, p<0.0001, T vs C) inheritance models. Our findings did not support an association between AXIN2 rs7224837 and IRF6 rs861019 polymorphism and risk/protection of NSCL/P. The IRF6 2235371 variant was not polymorphic in our population. Conclusion: The results indicate that the BMP4 rs17563 variant is likely to confer a protective effect against the occurrence of NSCL/P in a sample of the southeast Iranian population.

摘要 非综合征性唇裂伴或不伴腭裂（Non-syndromic cleft lip with or without palate, NSCL/P）是全球范围内常见的先天性畸形，病因复杂。现有研究提出，基因与环境因素的互作在该病的易感性中发挥作用。研究目的：本研究旨在探讨伊朗人群中AXIN2（轴抑制蛋白2，axis inhibition protein 2）rs7224837、BMP4（骨形态发生蛋白4，bone morphogenetic protein 4）rs17563、IRF6（干扰素调节因子6，interferon regulatory factor 6）rs861019及2235371多态性与NSCL/P的相关性。材料与方法：本病例对照研究纳入132名无亲缘关系的NSCL/P患者及156名健康对照者，采用聚合酶链反应-限制性片段长度多态性（polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP）法对上述遗传变异进行基因分型。结果：研究结果显示，BMP4 rs17563多态性在共显性（OR=0.36，95%CI=0.17~0.79，P=0.012，CT vs CC；OR=0.11，95%CI=0.01~0.88，P=0.019，TT vs CC）、显性（OR=0.30，95%CI=0.15~0.62，P=0.0007，CT+TT vs CC）、隐性（OR=0.12，95%CI=0.02~0.99，P=0.023，TT vs CC+CT）、超显性（OR=0.39，95%CI=0.18~0.84，P=0.021，CT vs CC+TT）及等位基因（OR=0.28，95%CI=0.15~0.55，P<0.0001，T vs C）遗传模型中，均显著降低NSCL/P的发病风险。本研究未发现AXIN2 rs7224837与IRF6 rs861019多态性与NSCL/P的发病风险或保护效应存在关联；IRF6 2235371变异在本研究人群中未呈现多态性。结论：本研究结果表明，在伊朗东南部人群样本中，BMP4 rs17563变异可能对NSCL/P的发生具有保护作用。