人趋化素样因子上游启动子区的单核苷酸多态性及其与哮喘的相关性  

Single Nucleotide Polymorphisms in the 5'-Upstream Sequence of Chemokine Like Factor and their Association with Asthma

作　　者：章巍[1] 何权瀛[1] 王广发[2] 赵红珊[3] 迟春花[2] 赵燕妮[2] 邓暄[3] 宿利[2] 孙遥摇[3] 王小迪[3] 

机构地区：[1]北京大学人民医院呼吸内科,北京100044 [2]北京大学第一医院呼吸内科,北京100034 [3]北京大学人类疾病基因研究中心,北京100083

出　　处：《中国呼吸与危重监护杂志》2009年第4期345-350,共6页Chinese Journal of Respiratory and Critical Care Medicine

摘　　要：目的寻找趋化素样因子(CKLF)基因上游启动子区的单核苷酸多态性(SNP),明确其与支气管哮喘发病的相关性。方法提取245例北京地区汉族人(其中哮喘患者119例,健康对照126例)基因组DNA,采用PCR方法扩增CKLF上游启动子区1553碱基的DNA片段并进行直接测序,分析发现的SNPs的等位基因频率、基因型频率和单倍型分布频率及其与哮喘的发病和临床表现的相关性。结果在CKLF上游启动子区共发现4个SNPs:SNP88(T>C)、SNP196(T>C)、SNP568(C>G)、SNP1047(C>G)。其等位基因频率分别为0.168(SNP88C)、0.168(SNP196C)、0.352(SNP568G)和0.167(SNP1047G),与以往报道的其他种族的结果明显不同。SNP88与SNP196之间、SNP88与SNP1047之间,以及SNP196与SNP1047之间存在完全连锁不平衡(D′=1.000,r2=1.000),SNP568与SNP88、SNP196及SNP1047间存在连锁不平衡(r2=0.366)。哮喘组与对照组4个SNPs的等位基因频率、基因型频率和单倍型频率差异无显著性。结论北京地区汉族人群CKLF编码基因上游调控区的基因多态性有其独特的分布特点及连锁不平衡特征,虽然与哮喘的发病无明显相关性,但其分布特点可能为其他疾病相关性研究提供有价值的资料。Objective To detect the single nucleotide polymorphisms （SNPs） in the upstream promoter region of chemokine like factor （CKLF） gene and analyze their possible associations with asthma and asthma-related phenotypes. Methods Direct Sequence of the 1553bp upstream promoter region of CKLF gene was performed in 245 Chinese Han human genomic DNAs （119 asthmatics and 126 controls）. The frequencies of alleles, genotypes, and haplotypes were determined and the association of these SNPs with asthma were further analyzed. Results Four novel SNPs, SNP88 （ T 〉 C） , SNP196 （ T 〉 C） , SNP568 （ C 〉 G） ,and SNP1047 （ C 〉 G） were found in the promoter region of CKLF. The frequency of rare allele was 0. 168 （ SNP88C ）, 0. 168 （ SNP196C ） , 0. 352 （ SNP568G ） and 0. 167 （ SNP1047G ）, respectively. Haplotypes ,their frequencies and the linkage disequilibrium coefficients between SNPs were constructed. Complete linkage disequilibrium （LDs） were observed between SNP88 and SNP196,SNP88 and SNP1047, as well as SNP196 and SNP1047 ,respectively （D＇ = 1. 000 ,r2 = 1. 000）. SNP568 was in partial LD with the other three SNPs （ r2 = 0. 366 ）. No association between asthma and the SNPs was observed. Conclusions Four SNPs in the regulatory region of CKLF in Chinese Han population were firstly identified. Although no significant correlation with asthma was revealed, the SNP and haplotype information is useful for other disease association studies in the future.

关 键 词：哮喘 趋化素样因子 单核苷酸多态性 启动子区 基因型 单倍型 

分 类 号：R562.25[医药卫生—呼吸系统]