摘要
目的先天性小耳畸形是我国第二高发的颅面部出生缺陷,以往针对先天性小耳畸形的研究多集中在手术治疗技术和流行病学调查方面,而对导致疾病发生的遗传因素研究极少。MEOX2基因是近些年来发现的同源盒基因,其编码的蛋白是核转录因子,能够激活或抑制其下游基因的表达。方法本研究采用候选基因关联研究的手段揭示其与先天性小耳畸形之间的关系。我们首先基于千人基因组计划数据挑选MEOX2基因的标签SNP,利用飞行时间质谱在328例小耳畸形患者和500例对照中进行了分型。结果发现了2个和小耳畸形显著关联(Bonferroni P<0.05)的位点,分别为rs76405124(P=0.006556,OR=0.82)和rs10224052(P=0.01619,OR=0.83)。采用Impute2进行基因组填充后分析又发现rs71549953亦与小耳畸形显著(Bonferroni P<0.05)相关。结论本研究不仅揭示了小耳畸形新的关联基因,还为该病的遗传病因学研究提供新视角。
Objective Congenital microtia was the second most common craniofacial anomaly in China. Most pre-vious studies on congenital microtia focused on surgical treatment techniques and epidemiology, while few considered genetic factors. As a homeobox gene, encoded protein of MEOX2 is a nuclear transcription factor that can activate or in-hibit the expression of its downstream genes. Studies based on pedigrees have identified mutations within homeobox genes as the causes of microtia. To add more knowledge on the relationship between homeobox gene and microtia. Methods We genotyped tag SNPs from MEOX2 in 328 microtia patients and 500 healthy controls. Results We found 2 significant （Bonferroni P＜0.05） microtia associated loci which were rs76405124 and rs10224052, respectively. We an-alyzed genotype imputation by Impute2 and found rs71549953 was another significant （Bonferroni P＜0.05） microtia associated loci. Conclusion Our research has not only revealed a new associated gene for microtia, but also provided new insight into the etiology of microtia.
作者
冯涛
钱瑾
王冰清
王悦
章庆国
FENG Tao;QIAN Jin;WANG Bingqing;WANG Yue;ZHANG Qingguo(Zhangjiakou Women and Children Hospital,Zhangjiakou,Hebei,75000;Chinese Academy of Medical Sciences Plastic Surgery Hospital,Beijing,100144)
出处
《中华耳科学杂志》
CSCD
北大核心
2018年第3期362-368,共7页
Chinese Journal of Otology
基金
国家自然科学基金项目(81372085
81571924
81701930)
81372085:利用两阶段法全基因组关联研究探寻我国非综合征型先天外中耳畸形的易感基因及功能研究
81571924:先天性外中耳畸形的基因环境交互作用研究
81701930:目标区域捕获测序探查与半侧颜面短小显著关联的染色体区域内的致病突变~~
