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GSTM1和GSTP1基因多态性与OSAHS合并COPD表型研究
A study on the correlation between the gene polymorphism of GSTM1 and GSTP1 and the phenotype of COPD combined with OSAHS
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DOI:
作者:
何正强
HE Zheng-qiang
作者单位:
深圳市人民医院 暨南大学第二临床医学院
ShenZhen people’s hospital, the Second Clinical Medical College of Ji’nan U-niversity
关键词:
重叠综合征;慢性阻塞性肺疾病;阻塞性睡眠呼吸暂停低通气综合征;谷胱甘肽硫转移酶 M1;谷胱甘肽硫转移酶 P1;基因多态性
overlap syndrome ;chronic obstructive pulmonary disease; obstructive sleep apnea hypopnea syndrome;glutathione S-transferase M1;glutathione S-transferase P1; gene polymorphism
摘要:
目的 探讨 GSTM1 和 GSTP1 基因多态性与OSAHS合并COPD表型(overlap syndrome,OS)的相关性。方法 收集2013 年 1月至 2015 年 3月深圳市人民医院门诊就诊或住院的OS、COPD和OSAHS患者各62例,62例健康体检者作为正常对照组,采用聚合酶链式反应(PCR)检测 GSTM1 基因多态性,且用 sanger 测序法检测其GSTP1 外显子 5 单核苷酸多态性。采用Hardy-Weinberg 平衡检验和χ2检验比较各组间等位基因和基因型频率,并根据临床资料进行相关性分析。结果 (1)GSTM1 基因表达型和缺失型分布频率分别为OS 组:52.23%和46.77%,COPD 组:59.68%和40.32%, OSAHS 组:35.48%和64.52%,正常对照组: 43.55%和56.45%,各组差异无统计学意义(P>0.05)。 GSTP1 基因 AA 型、 AG 型、GG型分布频率分别为OS组:62.91%、33.87%、3.22%,COPD组:75.81%、22.58%、1.61%,OSAHS组:64.52%、33.87%、1.61%,正常对照组:64.52%、33.87%、1.61%,各组差异无统计学意义(P>0.05)。(2)应用 logistic 回归分析 GSTM1 和GSTP1 基因型在OS中的交互作用,结果表明GSTM1 和GSTP1 基因型在OS发病中无交互作用。(3)应用多元线性回归分析结果显示GSTM1基因多态性与OS肺功能指标 FEV1 及FEV1/FVC 无相关性(P>0.05)。GSTP1基因多态性与OS肺功能 FEV1及FEV1/FVC均没有相关性(P>0.05)。结论 GSTM1基因和GSTP1 基因不是OSAHS合并COPD的易感基因,GSTM1基因型和GSTP1基因型与OSAHS合并COPD肺功能下降无相关。
Objective To investigate the relationship between the polymorphism of the GSTM1 and the GSTP1 genes and susceptibility to the phenotype of COPD combined with OSAHS(overlap syndrome,OS).Methods Patients came from outpatient or hospitalization of respiration department from January , 2013 to March, 2015, Afterwards we randomly divide them into OS group, COPD group,OSAHS group and normal control group,62 cases in each group. Normal control group from the clinic health examination at the same time.Each of them underwent pulmonary function test and polysomnography examination. Polymerase chain reaction (PCR) was used to detect GSTM1 gene polymorphism, sanger sequencing was used to sequencing of GSTP1 exon 5 to detect single nucleotide polymorphism, analysis of the relationship between gene polymorphisms of GSTM1 and GSTP1 and susceptibility to OS. Results (1)The frequency distribution of wild type and null type of GSTM1 gene were 52.23% and 46.77% in OS group, 59.68% and 40.32% in COPD group, 35.48% and 64.52% in OSAHS group , 43.55% and 56.45% in normal control group,the four groups had no significant difference by chi square test (P>0.05). The frequency distribution of AA, AG,GG genotype of GSTP1 were 62.91%, 33.87%,3.22% in OS group,75.81%,22.58%,1.61% in COPD group, 64.52%,33.87%,1.61% in OSAHS group and 64.52%,33.87%,1.61% in normal control group, the four groups had no significant difference by chi square test (P>0.05).(2)Logistic regression analysis was applied to analyse the interaction of GSTM1 and GSTP1 genotypes in OS through the comparison between OS group and normal group, not any genotype combinations was found to increase the risk of OS (P>0.05). This result showed there was no interaction between GSTM1 and GSTP1 genotype in OS.(3)Multivariate linear regression was used to analysis on the relationship of GSTM1 and GSTP1 gene polymorphism and pulmonary function in OS group and normal control group groups. The GSTM1 null genotype had no correlation with FEV1 and FEV1/FVC(P>0.05).The polymorphisms of GSTP1 had no correlation with FEV1 and FEV1/FVC(P>0.05).Conclusion The GSTM1 genotype and GSTP1 genotype were not susceptible genes of OS,and had negatively correlated with the decline of pulmonary function in OS.
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