[谷氨酸半胱氨酸连接酶调节亚基基因多态性与慢性阻塞性肺疾病易感性的关系]

[The relationship between the polymorphism of glutamate cysteine ligase modulatory subunit gene and the susceptibility to chronic obstructive pulmonary disease].

作者信息

Hu Rui-cheng, Tan Shuang-xiang, Dai Ai-guo

机构信息

Department of Respiratory Medicine, Hunan Institute of Gerontology, Hunan Province Geriatric Hospital, Changsha 410001, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2006 Feb;29(2):100-3.

PMID:16677451

Abstract

OBJECTIVE

To investigate whether glutamate cysteine ligase modulatory (GCLM) subunit gene polymorphism is associated with susceptibility to chronic obstructive pulmonary disease (COPD), and to study the relationship between polymorphism of GCLM gene with plasma gamma-glutamylcysteine synthetase (gamma-GCS) activity.

METHODS

Blood samples of 104 stable phase COPD smokers (COPD group), 124 healthy smokers (C group) and 132 healthy never-smokers (H group) were collected, and then the genotypes of GCLM -588C/T and GCLM -23C/T polymorphism sites were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP). The plasma gamma-GCS activity was measured by coupled enzyme procedure.

RESULTS

(1) The distribution of -588CC, -588CT, -588TT genotypes were corresponding to -23GG, -23GT, -23TT respectively in all of the individuals. (2) The frequencies of -588CC genotype and -588 C allele were significantly lower in COPD group (62.3% and 79.2%) than in C group (84.7% and 91.9%) and H group (78.8% and 89.0%, P < 0.01). (3) In smokers, GCLM -588 T allele carried a higher risk to COPD, the odds ratio (OR value) to C allele was 3.0, and with a 95% confidence interval 1.7 - 5.3. (4) The plasma gamma-GCS activity was increased in C group [(282 +/- 58) U/mg.prot] and COPD group [(224 +/- 54) U/mg.prot] as compared with H group [(157 +/- 26) U/mg.prot, P < 0.01], and were higher in healthy smokers than in COPD smokers (P < 0.01). (5) The smokers with -588CC genotype had higher gamma-GCS activity than CT or TT genotype [(292 +/- 54), (225 +/- 45) U/mg.prot, P < 0.01 in C group and (245 +/- 52), (188 +/- 36) U/mg.prot, P < 0.01 in COPD group], but the difference did not exist in H group [(158 +/- 27), (153 +/- 25) U/mg.prot, P > 0.05].

CONCLUSION

The polymorphism of GCLM -588C/T and -23G/T sites were associated with susceptibility to COPD, and were associated with plasma gamma-GCS activity.

摘要

目的

探讨谷氨酸半胱氨酸连接酶调节亚基（GCLM）基因多态性与慢性阻塞性肺疾病（COPD）易感性的关系，并研究GCLM基因多态性与血浆γ-谷氨酰半胱氨酸合成酶（γ-GCS）活性的关系。

方法

收集104例稳定期COPD吸烟者（COPD组）、124例健康吸烟者（C组）和132例健康非吸烟者（H组）的血样，采用聚合酶链反应（PCR）和限制性片段长度多态性分析（RFLP）检测GCLM -588C/T和GCLM -23C/T多态性位点的基因型。采用偶联酶法测定血浆γ-GCS活性。

结果

（1）所有个体中，-588CC、-588CT、-588TT基因型分别对应-23GG、-23GT、-23TT基因型。（2）COPD组-588CC基因型和-588 C等位基因频率（62.3%和79.2%）显著低于C组（84.7%和91.9%）和H组（78.8%和89.0%，P<0.01）。（3）在吸烟者中，GCLM -588 T等位基因患COPD的风险更高，与C等位基因的比值比（OR值）为3.0，95%置信区间为1.7 - 5.3。（4）与H组[（157±26）U/mg.prot，P<0.01]相比，C组[（282±58）U/mg.prot]和COPD组[（224±54）U/mg.prot]血浆γ-GCS活性升高，且健康吸烟者高于COPD吸烟者（P<0.01）。（5）-588CC基因型吸烟者的γ-GCS活性高于CT或TT基因型[C组中分别为（292±54）、（225±45）U/mg.prot，P<0.01；COPD组中分别为（245±52）、（188±36）U/mg.prot，P<0.01]，但H组中差异不存在[（158±27）、（153±25）U/mg.prot，P>0.05]。