去整合素金属蛋白酶33基因多态性与新疆维吾尔族人群支气管哮喘及其严重程度的关系

Relationship between disintegrin and metalloproteinase gene polymorphism of bronchial asthma and its severity in Uygur population

目的 探讨去整合素金属蛋白酶（ADAM）33基因多态性与新疆维吾尔族人群支气管哮喘（简称哮喘）及其严重程度的关系.方法 连续收集2009年1至12月在新疆医科大学第一附属医院就诊而明确诊断的的维吾尔族哮喘患者126例（哮喘组）,根据病情轻、重分为轻度组62例、中度组39例、重度组25例.以同期同族别且性别、居住地、年龄（相差5岁以内）相匹配的126名健康体检者为对照组.采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测各组ADAM33基因F＋1、S＋1、T1、T2和V4位点的多态性.结果 ADAM33基因T1、T2、V4位点基因型在哮喘组和对照组中分布差异有统计学意义（x2=8.064、8.013、11.737,P=0.018、0.018、0.003）.等位基因频数分布显示T1（C）、T2（A）、V4（G）位点均增加了哮喘发生的相对危险度（OR=2.080、2.139、1.912）.T1（TT和TC）、T2（GG和AG）和V4位点（GG和CC）基因型在轻、中、重度哮喘患者中分布频率差异均有统计学意义（均P ＜0.05）.连锁不平衡分析显示哮喘组中Hap4（CACAC）、Hap5（TACAG）显著高于对照组（9.6％比4.8％、6.8％比2.8％）（x2=4.545、4.377,P=0.033、0.036）,Hap2（CATGC）显著低于对照组（20.4％比30.4％）（x2=6.597,P=0.010）.结论 ADAM33基因T1、T2、V4位点多态性可能与新疆维吾尔族人群哮喘及其严重程度有关,维吾尔族群体中可能有哮喘易感的单体型或保护性的单体型存在.

Objective To explore the relationship between disintegrin and metalloproteinase （ADAM33） gene polymorphism of bronchial asthma and its severity in Xinjiang Uygur population.Methods From January to December 2009,a total of 126 consecutive Uighur asthmatics with a definite diagnosis at First Affiliated Hospital of Xinjiang Medical University were assigned into intermittent mild （n =62）,moderate （n =39） and severe （n =25） groups according to the severity of illness.The control group was a 1：1 paired population from healthy subjects matched similarly with regards to gender,race,residence and age （with a difference 〈5 years）.The ADAM33 gene polymorphisms of F ＋ 1,S ＋ 1,T1,T2 and V4 locus allele in each group were tested by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）.Results In ADAM33,the distribution of T1,T2 and V4 locus allele in asthmatics and controls had a significant difference （x2 =8.064,P=0.018;x2 =8.013,P=0.018 and x2=11.737,P=0.003）.The distribution of allelic frequency showed that all T1 （C）,T2 （A） and V4 （G） locus allele increased the relative risk degree of asthmatics （OR =2.080,2.139 and 1.912）.The distribution frequency of T1 （TC and TT）,T2 （AG and GG）,V4 （GG and CC） genotypes in mild,moderate and severe groups had significant differences （all P 〈 0.05）.Linkage disequilibrium analysis showed that in asthmatics,the presence of Hap2 （CATGC） was much lower than controls （20.4% vs 30.4% ; x2 =6.597,P =0.010） while Hap4 （CACAC） and Hap5 （TACAG） were much higher than those in controls （9.6% vs 4.8% and 6.8% vs2.8%;x2=4.545,P=0.033 and x2 =4.377,P=0.036）.Conclusions The ADAM33 gene polymorphism of T1,T2 and V4 locus allele may be associated with asthma and its severity in Xinjiang.And Uighur population may have both susceptible and protective haplotypes of asthmatics.