全基因组芯片扫描研究SLC7A1基因与先天性肥厚性幽门狭窄的相关性  

Genome-wide association study on the relationship between SLC7A1 gene and congenital hypertrophic pyloric stenosis

作　　者：刘涛[1] 许文敏 冯志强[1] 聂玉强[1] 张又祥[2] Liu Tao;Xu Wenmin;Feng Zhiqiang;Nie Yuqiang;Zhang Youxiang(Department of Gastroenterology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510182, China;Department of Pediatrics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510182, China)

机构地区：[1]广州医科大学附属广州市第一人民医院消化内科,510182 [2]广州医科大学附属广州市第一人民医院儿科,510182

出　　处：《中华生物医学工程杂志》2019年第3期274-278,共5页Chinese Journal of Biomedical Engineering

基　　金：广东省医学科学技术研究基金(A2016318);广东省自然科学基金(S2012040007771).

摘　　要：目的在全基因组范围内探讨先天性肥厚性幽门狭窄(CHPS)发病的相关候选基因。方法采用两步法进行相关基因筛选。第一步,选择2006年8月至2010年10月就诊于广州市第一人民医院的CHPS患儿及其父母双亲组成的核心家系为研究对象,所有入选者均为汉族。采用Affymetrix公司的SNP6.0芯片进行全基因组芯片扫描,初步筛选相关候选基因。第二步,对在第一步筛选出的候选基因相关SNP位点,扩大样本进行PCR及测序,应用传递不平衡检验(TDT)进行分析,进一步验证其基因型与CHPS的相关性。结果共有894135个SNP在所有23个核心家系成员中被扫描出来,总体扫描成功率达98.63%,有多个基因与CHPS发病相关,对其中的SLC7A1基因(位于13q12.3)进行进一步验证,选择其中rs476506位点,对40个核心家系进行PCR及测序方法进行验证,测序结果TDT分析显示其与CHPS发病相关(χ^2=11.524,P=0.0007)。结论SLC7A1基因多态性位点rs476506与中国汉族人群CHPS发病相关,SLC7A1基因可能为中国汉族人群CHPS发病候选基因。Objective To investigate the candidate genes related to the pathogenesis of congenital hypertrophic pyloric stenosis (CHPS) in the whole genome. Methods A two-step method was used to screen the related genes.(1) Trios composed by the core family of CHPS children and their parents, who presented to Guangzhou First People’s Hospital between August 2006 and October 2010, were selected as subjects. All the subjects were of Han ethnicity. SNP 6.0 (Affymetrix) was used for genome-wide microarray to preliminarily screen out the related candidate genes.(2) For the candidate gene-related SNPs screened in the first step, the samples were amplified for PCR and sequencing, and analyzed by transfer disequilibrium test (TDT) to further verify the correlation between genotype and CHPS. Results A total of 894 135 SNPs were scanned out from 23 core family members, yielding an overall successful scan rate of 98.63%. Several genes were found to be associated with the pathogenesis of CHPS. The SLC7A1 gene (13q12.3) was further studied by validating its rs476506 locus in the 40 core family trios through PCR and sequencing. TDT analysis confirmed that rs476506 is associated with CHPS (χ^2=11.524, P=0.0007). Conclusion In Chinese Han population, SLC7A1 gene polymorphism at rs476506 locus is associated with pathogenesis of CHPS, and therefore can be a candidate gene for CHPS.

关 键 词：先天性肥厚性幽门狭窄 SLC7A1基因 rs476506 全基因组芯片扫描分析 

分 类 号：R725.7[医药卫生—儿科]