细胞间黏附分子-1基因K469E多态性与慢性阻塞性肺疾病的相关性

Association of intercellular adhesion molecule-1 gene K469E polymorphism with chronic obstructive pulmonary disease

目的:探讨细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)基因K469E多态性与中南地区汉族人群慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的相关性及对ICAM-1的影响。方法:从来自中南地区、主要是湖南地区的汉族人群中收集COPD患者91例及健康对照者80例的血液标本,提取基因组DNA,用PCR方法扩增包含K469E位点的碱基序列后进行测序确定基因型;从完成测序的对象中随机抽取COPD患者60例、正常对照者26例的血清进行可溶性细胞间黏附分子-1(soluable intercellular adhesion molecule-1,sICAM-1)的检测。结果:COPD患者的基因型及等位基因分布频率与正常对照组差异没有统计学意义(P>0.05);但在16例极重度患者中,KE+EE基因型和E等位基因频率相对于75例非极重度患者增高(10/16 vs 26/75,12/30 vs 20/150,P<0.05)。COPD组的sICAM-1水平较对照组增高[(213.8±35.6)ng/mL vs(175.8±22.7)ng/mL,P<0.05],并且与第1秒用力呼气容积占预计值的百分比(forced expiratory volume in one second for the percentage of predicted value,FEV1%)呈负相关(r=-0.591,P<0.01);但正常对照组和不同严重程度COPD亚组中,KE+EE基因型与KK基因型间sICAM-1水平比较差异无统计学意义(P>0.05)。结论:ICAM-1基因K469E多态性与中南地区汉族人群COPD的发病没有明显相关性;但携带E等位基因可能是病情严重程度的危险因素。

Objective： To test the association of K469E,the common intercellular adhesion molecule-1（ICAM-1） polymorphism with chronic obstructive pulmonary disease（COPD） and expression of ICAM-1 in Han people of Central and South Region in China. Methods： A case-control study was done on 91 patients with COPD and 80 matched controls of Han people from central and south region in China,mainly from Hunan Province.Genomic DNA was extracted from white blood cells.ICAM-1 sequences were amplified by PCRand analyzed by agarose gel electrophoresis.Genotypes were defined by base sequencing.In addition,soluable intercellular adhesion molecule-1（sICAM-1） serum levels were measured in 86 people picked out randomly from the COPD group and the control group. Results： There was no difference in the frequency of the genotype and allele between the COPD group and the controls,but compared with those who were not very severe,the frequency of KE/EE genotypes and E allele in COPD patients at very severe stage was significantly higher（10/16 vs 26/75,12/30 vs 20/150,P0.05）.The level of sICAM-1 increased in the COPD patients,with negative correlation to forced expiratory volume in one second for the percentage of predicted value（FEV1%）.But in both COPD patients and controls,the level of sICAM-1 did not differ significantly in different genotypes（P0.05）. Conclusion： K469E polymorphism of ICAM-1 may not affect the susceptibility of COPD and the expression of ICAM-1 in Han people from central and south of China in this study,but carriers of E allele are at high risk of developing severe stage of COPD.