乙二型腎上腺素接受體基因多型性變化在國人慢性阻塞性肺疾病的研究

Polymorphism of the ß2-adrenoceprot in Chronic Obstructive Pulmonary Disease in Chinese Subjects

韓鴻志(Horng-Jyh Harn) ； 陳穎信(Hsaio-Dung Liu) ； 劉曉東(Shi-Jye Chu):朱士傑(Ying-Hsin Chen)藍國徵(Kuo-Cheng Lan):劉敏英(Ming-YIng Liu)

《中華民國急救加護醫學會雜誌》 11卷2期 (2000/06) Pp. 69-78

https://doi.org/10.30018/JECCM.200006.0003

摘要

The ß2-adrenoceprot (ß2-AR) agonists are used frequently in the treatment of COPD. Nine polymorphisms , in the ß2-AR gene have been described. There loci at amino acid position 16, 27 and 164(Arg16-Gly16, Gln 27Glu27 and Thr 164- Ile164) have been found to alter recetor funcion. The first two are also disease-modifying in subjects with asthma. However the contrbution of these polymorphisms to the development of chronic obstructive pulmonary disease (COPD)remains to be eastablished. We examined the gene encoding the ß2-AR to assess the frequency of these three plymorphicms in 65 patients with COPD and 41 normal subjects. Polymorphisma of the ß2-Arcoding block were delineated using an allelespecific PCr approach. The allele –specific PCR technique was verified by direct dedeoxy sequencing of genotype variant and pulmonary function had been analyzed by chi-square test. The incidence of Arg16 ß2-AR homozygous polymorphisms (or allele frequency0wad greater in COPD partients than normal control (P=0.01). However, the incidence of Gln27 and Thrl64 ß2-AR polymorphisms were not different between COPD patients and normal control (P=0.571 and P=0.930 respective ). Further, we divided the patients into 3 groups acc ording to their percent predictedjvalue of Forced Expiratory Volume in 1 secualue(FEV1%): fevi＜35% of predicted value (vey serere), FEVI.. 35%-49%(sercer), FEVI＞50%(moderately serere or less). We found a signficant correlation between Glin 27 ß2-AR polymorphism and FEVI1% value (P＜0.018 ). A trrend of Gln\Gln homozygosity wad observed more frequently in patients with serere and moderately serere ir kess FEVU vakyes. In con clusion, the polymorphism loci at amino acid position 16 are related to COPD occurrence. The glutamine 27 ß2-AR polymorphism apperas to contribute to severe COPD in chinese.

關鍵字

乙二型腎上線腺素接受體 ； 慢性阻塞性肺疾病 ； 多型性 ； 第一秒強迫呼氣體積 ； 專一性對偶基因聚合酶連鎖反應

並列摘要

The ß2-adrenoceprot (ß2-AR) agonists are used frequently in the treatment of COPD. Nine polymorphisms , in the ß2-AR gene have been described. There loci at amino acid position 16, 27 and 164(Arg16-Gly16, Gln 27Glu27 and Thr 164- Ile164) have been found to alter recetor funcion. The first two are also disease-modifying in subjects with asthma. However the contrbution of these polymorphisms to the development of chronic obstructive pulmonary disease (COPD)remains to be eastablished. We examined the gene encoding the ß2-AR to assess the frequency of these three plymorphicms in 65 patients with COPD and 41 normal subjects. Polymorphisma of the ß2-Arcoding block were delineated using an allelespecific PCr approach. The allele –specific PCR technique was verified by direct dedeoxy sequencing of genotype variant and pulmonary function had been analyzed by chi-square test. The incidence of Arg16 ß2-AR homozygous polymorphisms (or allele frequency0wad greater in COPD partients than normal control (P=0.01). However, the incidence of Gln27 and Thrl64 ß2-AR polymorphisms were not different between COPD patients and normal control (P=0.571 and P=0.930 respective ). Further, we divided the patients into 3 groups acc ording to their percent predictedjvalue of Forced Expiratory Volume in 1 secualue(FEV1%): fevi＜35% of predicted value (vey serere), FEVI.. 35%-49%(sercer), FEVI＞50%(moderately serere or less). We found a signficant correlation between Glin 27 ß2-AR polymorphism and FEVI1% value (P＜0.018 ). A trrend of Gln\Gln homozygosity wad observed more frequently in patients with serere and moderately serere ir kess FEVU vakyes. In con clusion, the polymorphism loci at amino acid position 16 are related to COPD occurrence. The glutamine 27 ß2-AR polymorphism apperas to contribute to severe COPD in chinese.

並列關鍵字

The ß2-adrenoceprot (ß2-AR) ； chronic obstruction pulmonary disease(COPD) ； Apolymorphism ； Forced Expiratory Volume in 1 sec value (fevi%) ； Allele-specific polymerase chain reaction (PCR)