谷氨酰半胱氨酸连接酶调节基因多态性与慢性阻塞性肺疾病易感性的关系

目的探讨谷氨酰半胱氨酸连接酶调节(GCLM)基因多态性与血浆γ谷氨酰半胱氨酸合成酶(γGCS)活性及慢性阻塞性肺疾病(COPD)易感性的关系。方法应用聚合酶链反应(PCR)及限制性片段长度多态性分析(RFLP)方法检测106例稳定期吸烟的COPD患者(COPD组)、124名健康吸烟者(C组)及132名健康不吸烟者(H组)GCLM基因-588C/T和-23G/T多态性位点基因型,并用双酶法检测血浆γGCS活性。结果-588CC与-23GG、-588CT与-23GT、-588TT与-23TT基因型在个体间分布一致。COPD组-588位点CC基因型和C等位基因频率(62.3%、79.2%)显著低于C组(84.7%、91.9%)和H组(78.8%、89.0%,P均<0.01)。吸烟者-588T等位基因相对于C等位基因患COPD的比值比(OR值)为3.0,95%可信区间为1.7～5.3。C组[(282±58)U/mg·prot]和COPD组[(224±54)U/mg·prot]血浆γGCS活性显著高于H组[(157±26)U/mg·prot,P<0.01],其中C组高于COPD组(P<0.01)。H组-588CC与CT/TTγGCS活性比较差异无统计学意义[(158±27)、(153±25)U/mg·prot,P>0.05],而C组[(292±54)、(225±45)U/mg·prot]和COPD组[(245±52)、(188±36)U/mg·prot]中-588CCγGCS活性显著高于CT/TT(P<0.01)。结论GCLM-588C/T、-23G/T位点多态性与血浆γGCS活性及COPD易感性相关。

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

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.