中国北方汉族人基质金属蛋白酶1、9、12基因多态性与慢性阻塞性肺疾病易感性的研究

Study on matrix metalloproteinase 1, 9, 12 polymorphisms and susceptibility to chronic obstructive pulmonary disease among Han nationality in Northern China

目的探讨基质金属蛋白酶(matrix metalloproteinases,MMPs)基因多态性与慢性阻塞性肺疾病(COPD)易感性的关系。方法采用病例对照研究方法,收集147例吸烟COPD患者和120 名吸烟非COPD正常对照。调查研究对象的性别、年龄、吸烟史、职业粉尘接触史、临床症状、体格检查、测定肺通气功能和支气管舒张试验。应用聚合酶链反应、限制性内切酶分析法比较MMP-9 (-1562 C/T)、MMP-1(-1607 1G/2G)、MMP—12(-82 A/G)、MMP-12(-357 Asn/Ser)基因多态性在COPD 组和吸烟非COPD对照组的差异。结果MMP-12基因型Asn/Asn和CT/AsnAsn可增加患COPD的危险性。OR值分别为2.361(95%CI:1.369～4.017)和2.433(95%CI:1.159～5.342);CC/1G1G/ SerSer对COPD患病有保护作用。OR值为0.457(95%CI:0.231～0.911)。结论CT和AsnAsn两基因型同时存在,可增加COPD的易感性,CC、GG和SerSer三基因型同时存在对患COPD有防护作用;多基因联合作用对多基因遗传病发病的影响比单个易感基因的作用更重要。

Objective To study the association between the functional polymorphism of matrix metalloproteinases（MMPs） and the development of chronic obstructive pulmonary disease （COPD）. Methods 147 COPD patients and 120 healthy smoking controls were selected. Spirometry and chest X-rays had been taken. Questionnaires including sex, age, smoking history, occupational exposure were completed. MMP-9 （-1562 C/T）, MMP-1（-1607 1G/2G）, MMP-12 （-82 A/G）, MMP-12（-357 Asn/ Ser） alleles were determined using PCR-RFLP method. Independent samples T test analysis was carried out to compare patients＇ age, smoking index, FEVI/FVC,FEV~ % pred with that of healthy controlled group. The frequencies of genotypes and alleles between groups were analyzed by chi-square tests and multilogistic regression. Results MMP12 Asn/Asn,CT/AsnAsn were risk factors for smoking-induced COPD. The ORs were 2.361 （95% CI：1.369-4.017） and 2.433（95% CI：1.159-5.342） respectively while CC/1G1G/ SerSer seemed to be a protective factor for smoking-induced COPD, with OR as 0.457 and 95% CI as 0.231-0.911. Conclusion Asn/Asn, CT/AsnAsn might be susceptible genotypes while CC/GG/SerSer might serve as protective genotype.