谷胱甘肽转硫酶基因多态性与湖北汉族人群溃疡性结肠炎的关系

Correlation between generic polymorphisms of glutathione S-transferases and ulcerative colitis in Hubei Han population

目的 探讨谷胱甘肽转硫酶（GSTs）基因多态性与湖北汉族人群溃疡性结肠炎（UC）的关系.方法 回顾性分析2002年8月至2009年12月武汉大学中南医院、武汉大学人民医院、华中科技大学附属同济医院和协和医院收治的270例湖北汉族UC患者（UC组）及同期623例健康体检者（对照组）的临床资料.根据病变范围将UC患者分为远端UC组（229例）和广泛UC组（41例）;根据病变严重程度将UC患者分为轻中度组（237例）和重度组（33例）.采用聚合酶链反应检测GSTM1和GSTT1的基因多态性、采用限制性片段长度多态性聚合酶链反应检测GSTP1的基因多态性,并对GSTs基因型进行判定.将含有157 bp片段和480 bp片段者分别定义为GSTM1（＋）和GSTT1（＋）,而无相应的扩增产物者分别定义为GSTM1（-）、GSTT1（-）.采用x2检验对数据进行分析.结果 UC组和对照组中GSTM1（-）、GSTT1（-）和GSTP1纯合子突变型基因型（Val/Val）的分布频率分别为70.7%（191/270）、64.8%（175/270）、48.9%（132/270）和41.7%（260/623）、47.2%（294/623）、34.3%（214/623）,两组比较,差异有统计学意义（x2=63.404,22.320,25.384,P＜0.05）.进一步根据UC临床症状进行分层分析,远端UC组和广泛UC组中GSTT1（-）、GSTP1（Val/Val）的分布频率分别为71.6%（164/229）、57.6%（132/229）和31.7%（13/41）、29.3%（12/41）,两组比较,差异有统计学意义（x2=24.528,9.609,P＜0.05）.远端UC组与广泛UC组的GSTM1（-）基因型的分布频率分别为65.1%（149/229）和56.1%（23/41）,两组比较,差异无统计学意义（x2=1.210,P＞0.05）.远端UC组和广泛UC组中GSTT1（-）和GSTP1（Val/Val）的分布频率分别为71.6%（164/229）、31.7%（13/41）和57.6%（132/229）、29.3%（12/41）,两组比较,差异有统计学意义（x2=24.528,9.609,P＜0.05）.轻中度UC组和重度UC组中GSTM1（-）、GSTT1（-）、GSTP1（Val/Val）分布频率比较,差异无统计学意义（x2=0.623,1.884,3.403,P＞0.05）.结论 突变的GSTs基因型与湖北汉族人群的UC发生明显相关.GSTs突变基因型可能与UC患者病情严重程度无关.

Objective To investigate the correlation between genetic polymorphisms of glutathione S-transferases （GSTs） and ulcerative colitis （UC） in Hubei Han population. Methods Genetic polymorphisms of GSTM1 and GSTT1 of 270 patients with UC （UC group） who were admitted to the Zhongnan Hospital, People＇s Hospital of Wuhan University, Tongji Hospital and Union Hospital of Huazhong University of Science and Technology from August 2002 to December 2009 and 623 healthy people （ control group） were detected by restriction fragment length polymorphism-polymerase chain reaction. All UC patients were allocated to distal UC group （n= 229） and extensive UC group （n =41 ） according to the location of the lesions; and all UC patients were also allocated to mild-moderate group （n = 237） and severe group （n = 33 ）. The genetic polymorphisms of GSTP1 of these patients and healthy people were detected by polymerase chain reaction. The genotypes of GSTM1, GSTT1 and GSTP1 were also detected. GSTM1 and GSTT1 containing small DNA segments （ 157 bp and 480 bp） were defined as GSTM1 （＋） and GSTT1 （＋）, otherwise, GSTM（-） and GSTT1 （-）, respectively. All data were analyzed by chisquare test. Results The frequencies of GSTM1（-）, GSTT1（-） and GSTP1 （Val/Val） were 70.7% （191/270）,64.8% （175/270） and 48.9% （132/270） in the UC group, and 41.7% （260/623）, 47.2% （ 294/623 ） and 34.3% （214/623） in the control group, with a significant difference between the two groups （x2 = 63. 404,22. 320, 25. 384, P ＜0.05 ）. The frequencies of GSTT1 （-） and GSTP1 （Val/Val） were 71.6% （164/229） and 57.6% （132/229） in the distal UC group, which were significantly higher than 31.7% （13/41） and 29.3%（ 12/41 ） in the extensive UC group （ x2 = 24.528, 9.609, P ＜ 0.05 ）. The frequencies of GSTM1 （-） were 65.1%（149/229） in the distal UC group and 56.1% （23/41） in the extensive UC group, with no significant difference between the two groups （ x2 = 1. 210, P ＞ 0.05 ）. The frequencies of GSTT1 （-） and GSTP1 （ Val/Val ） were 71.6%（164/229）, 31.7% （ 13/41 ） in the distal UC group and 57.6% （ 132/229）, 29.3% （ 12/41 ） in the extensive UC group, with a significant difference between the two groups （ x2 = 24. 528, 9. 609, P ＜ 0. 05 ）. There was no significant difference in the frequencies of GSTM1 （-）, GSTT1 （-）, GSTP1 （Val/Val） in the mild-moderate group and the severe group（ x2 = 0. 623, 1. 884, 3. 403, P ＞ 0. 05 ）. Conclusions Variant genotypes of GSTs are significantly correlated with UC in Hubei Han population. The severity of UC may not be correlated with variant genotypes of GSTs.