不同个体对高原低氧反应适应性与谷胱苷肽转移酶Pi基因多态性的关系

Relationship between adaptation to high altitude hypoxia environment and glutathione S-transferase Pi gene polymorphism in different individuals

目的:以平原汉族人群为对照,对登山运动员谷胱苷肽转移酶Pi基因多态性进行检测,分析谷胱苷肽转移酶Pi基因多态性与机体适应高原低氧环境的关系。方法:实验于2005-04/06在西藏抽取86名登山运动员血样作为高原组,在广州抽取90名解放军体育学院健康汉族学员的血样作为平原对照组。采用聚合酶链反应-限制性片段长度多态性分析技术检测两组人群体内谷胱苷肽转移酶Pi基因的多态性,同时用分光光度法测定谷胱苷肽转移酶的活性,并分析两组谷胱苷肽转移酶Pi基因多态性与谷胱甘肽转移酶活性之间的关系。结果:按意向处理分析,176名受试者的检测数据全部进入结果分析。①基因型测定结果:Alw26I限制性内切酶酶切后,产生如下不同的酶切片段:328bp,222bp,106bp和105bp(后两者混为一条带)四条带者为变异的杂合子等位基因型AG;222bp,106bp和105bp三条带者为变异的纯合子等位基因型GG;328bp,106bp和105bp三条带者为野生性的纯合子等位基因型AA。②谷胱苷肽转移酶活性的检测结果:谷胱苷肽转移酶Pi变异基因型和野生基因型的个体,其谷胱苷肽转移酶的活性均比平原组高眼(151.06±11.37),(141.04±13.40);(177.11±11.78),(159.01±16.49)U/mL;P<0.001演。③两组谷胱苷肽转移酶Pi基因多态性测定结果:高原组3种基因型(AA,AG和GG)的频率分别为73.3%,25.6%和1.16%,其中有23人为变异基因型,A和G基因频率分别为86%和14%。平原对照组3种基因型的频率分别为55.6%,42.2%和2.22%,有40人为变异基因型,A和G基因频率分别为77%和23%。高原组谷胱苷肽转移酶Pi变异基因型频率明显低于平原组,分别为26.7%和44.4%(χ2=5.99,P=0.011)。结论:谷胱苷肽转移酶Pi野生基因型在高原环境中表现出选择性优势,可能与不同个体对高原低氧反应的敏感性不同有关。

AIM： To investigate the relationship between glutathione S-transferase Pi （GSTP1） gene polymorphism and human body adaptation to high altitude hypoxia environment through analysis glutathione S-transferase Pi gene polymorphism in Tibetan mountaineers compared with sea level Han Chinese. METHODS： The experiment was completed from April to June 2005. Eight-six Tibetan mountaineers＇ peripheral blood samples were collected in Tibet and attributed to high altitude group. Ninety sea-level Han Chinese＇s peripheral blood samples were collected in Guangzhou and used as control group. Glutathione S-transferase Pi gene polymorphism was examined in two groups using polymerase chain reaction and restriction fragment length polymorphism, meanwhile the activity of glutathione S- transferase was also determined by spectrophotometer, and their correlations with genetic polymorphisms and activity of glutathione S- transferase in two groups were observed. RESULTS： All examined datum in 176 subjects were involved in the result analysis according to intention-to-treat analysis. ① Result of glutathione S-transferase Pi genotypes： The polymerase chain reaction product of glutathione S-transferase Pi gene was digested with Alw26I enzyme and the digested fragments were 328 bp, 222 bp, 106 bp and 105 bp for heterozygote variant alleles AG, 222 bp, 106 bp and 105 bp for homozygous variant alleles GG, 328 bp 106 bp and 105 bp for homozygous wild alleles AA. ②Result of activity of glutathione S-transferase in two groups： The enzyme activity of glutathione S-transferase in Tibetan mountaineers with glutathione S-transferase Pi mutant genotype and wild genotype were higher than those of control group [（151.06±11.37）, （141.04±13.40）; （177.11±11.78）, （159.01±16.49）U/ml;P 〈 0.001].③ Result of glutathione S-transferase Pi gene polymorphisms in two group： Three genotypes （AA, AG and GG） frequencies in altitude group were 73.3%, 25.6% and 1.16%, and in sea-level group were 55.6%, 42.2% and 2.22%, respectively. The glutathione S-transferase Pi mutant genotypes were found in 23 of 86 Tibetan mountaineers and 40 of 90 sea-level Han Chinese. The A and G gene frequencies were 86% and 14% in Tibetan mountaineers, 77% and 23% in control group, respectively. The proportion of glutathione S-transferase Pi mutant genotypes was significantly lower in the Tibetan mountaineers than that of control subjects （26.7% vs. 44.4%） （x^2=-5.99, P 〈 0.05）. CONCLUSION： Glutathione S-transferase Pi wild genotype shows selective advantage in the setting of altitude hypoxic challenge, and its genotypes may be related with the different susceptibility of response to high altitude hypoxia.