Guo Qiang, Li Dongmei, Meng Xiangbiao, Liu Tingting, Shi Jinna, Hao Yanru, Jiao Xiaohui, Lv Kewen, Hu Tenglong, Song Tao
Department of Stomatology Scientific Research Management Office, The First Affiliated Hospital, Harbin Medical University, Nangang District, Harbin, China.
Medicine (Baltimore). 2017 May;96(19):e6724. doi: 10.1097/MD.0000000000006724.
Nonsyndromic orofacial clefts (NSOC) are the most common orofacial congenital defect with a complex etiology. Genome-wide association studies have identified paired box protein 7 (PAX7) and netrin-1 (NTN1) as candidate susceptibility genes for NSOC in both European and Asian populations. Here, possible associations between single-nucleotide polymorphisms (SNPs) in or near PAX7 and NTN1 were investigated in relation to risk of NSOC in a northern Chinese population.
A total of 602 individuals with NSOC and 510 controls were recruited from northern China. Polymerase chain reaction-ligation detection reactions were used to analyze 4 SNPs (rs742071, rs6659735, rs766325, and rs4920520) of PAX7 and 2 SNPs (rs9904526 and rs9788972) of NTN1. Investigations of polymorphisms and risk of NSOC were conducted by using the PLINK software.
NTN1 rs9788972 AG was found to be associated with an increased risk of NSOC compared to the GG homozygous genotype (OR = 1.43, 95% CI = 1.11-1.86, P = .006). When the multifactor dimensionality reduction method was applied, NTN1 rs9788972 still exhibited an increased risk for NSOC (P = .008). In contrast, SNPs in PAX7 were not associated with any increased risk of NSOC.
NTN1 rs9788972 is identified as a risk locus for NSOC susceptibility in a northern Chinese population.
非综合征性口腔颌面部裂隙（NSOC）是最常见的口腔颌面部先天性缺陷，其病因复杂。全基因组关联研究已确定配对盒蛋白7（PAX7）和网蛋白1（NTN1）是欧洲和亚洲人群中NSOC的候选易感基因。在此，研究了中国北方人群中PAX7和NTN1及其附近单核苷酸多态性（SNP）与NSOC风险之间的可能关联。
从中国北方招募了602例NSOC患者和510例对照。采用聚合酶链反应-连接检测反应分析PAX7的4个SNP（rs742071、rs6659735、rs766325和rs4920520）以及NTN1的2个SNP（rs9904526和rs9788972）。使用PLINK软件进行多态性和NSOC风险的研究。
与GG纯合基因型相比，发现NTN1 rs9788972 AG与NSOC风险增加相关（OR = 1.43，95% CI = 1.11 - 1.86，P = 0.006）。当应用多因素降维方法时，NTN1 rs9788972仍显示NSOC风险增加（P = 0.008）。相比之下，PAX7中的SNP与NSOC风险增加无关。
在中国北方人群中，NTN1 rs9788972被确定为NSOC易感性的一个风险位点。
