Analysis of glutathione S-transferase M1 and glutathione S-transferase T1 gene polymorphisms suggests age-related relationships in a northern Italian population

The present work attempts to determine the distribution of GSTM1 and GSTT1 genotype and allele frequencies in a sample of northern Italian population, and to examine the age-related association of these polymorphisms. The frequencies of the deleted GSTM1 and GSTT1 genotypes were 0.357 and 0.169, respectively. GSTT1 null-genotype frequency found in this work further confirms data obtained in previous studies of Italian populations, while for GSTM1 deletion our sample showed a significantly lower-frequency value with respect to other Italian and European populations, with exception of the Greek. No significant differences occurred between men and women in the frequency of each gene, which could suggest that, in the studied sample, there were no sex differences in susceptibility to diseases and in detoxifying enzymes such as GSTs. In order to analyze the relationship between GSTT1 and GSTM1 gene polymorphisms and age, the sample was subdivided into four age groups: 1–30 years (n = 101); 31–50 years (n = 160); 51–79 years (n = 144) and 80–100 years (n = 58). This age-related analysis showed a decreasing gradient of GSTs null genotypes between younger and older groups, with the 80–100 age group showing a significantly lower frequency of GSTT1 null, GSTM1 null and GSTT1/GSTM1 double null genotypes with respect to the younger group.     

Glutathione S-transferase GSTM1 and GSTT1 null genotypes as potential risk factors for urothelial cancer of the bladder

 Onehundred-and-thirteen patients with cancer of the urinary bladder (cases) were examined with respect to the frequency of null genotypes of the polymorphic glutathione S-transferases GSTM1 and GSTT1. The allelic background in the German population of the area was evaluated by analysing 170 newborns (controls). The frequency of GSTM1 and GSTT1 null genotypes in this population, using methods based upon internal standard controlled polymerase chain reaction (PCR), was 0.54 and 0.18 respectively. An elevated relative bladder cancer risk of GSTM1 null genotype carriers was indicated by comparison of this background with the data of the bladder cancer cases (OR = 1.81; 95% CI [1.10, 2.98]; p = 0.019). The frequencies of the GSTT1 null genotype in the total group of bladder cancer cases versus controls did not differ statistically. However, a significantly higher relative risk of bladder cancer for the GSTT1 null genotype was detected in the cases-subgroup of non-smokers (OR = 3.84; 95% CI [1.21, 12.23]; p = 0.023). Thus, the GSTT1 null genotype might represent a minor risk factor for human bladder cancer which should be further investigated. Received: 2 May 1996 / Accepted: 16 July 1996     

Glutathione transferase T1 and M1 genotype polymorphism in the normal population of Shanghai

Glutathione transferases are known to be important enzymes in the metabolism of xenobiotics. In humans genetic polymorphisms have been reported for the hGSTM1 and hGSTT1 genes leading to individual differences in susceptibility towards toxic effects, such as cancer. This study describes the distribution of the two polymorphisms of hGSTT1 and hGSTM1 in the normal Chinese population of Shanghai. Out of 219 healthy individuals having been genotyped for GSTT1 and GSTM1, 108 (49%) were identified to be homozygously deficient for the GSTT1 gene and 107 (49%) for the GSTM1 gene. Received: 26 January 1998 / Accepted: 8 April 1998     

谷胱甘肽转移酶T1基因型与苯中毒遗传易感性

目的　探讨谷胱甘肽转移酶T1(GSTT1)基因多态与苯中毒遗传易感性的关系。方法　应用聚合酶链式反应 (PCR)方法对 3 5例苯中毒病例、44例苯作业工人及 2 6例正常对照组的GSTT1的基因型进行了检测。结果　苯中毒患者组GSTT1缺失基因型频率为 60 % ,明显高于正常对照组的 46 15 %和苯作业工人组的 40 91% ,但未出现统计学意义(P >0 0 5 )。结论　GSTT1基因多态与苯中毒遗传易感性无关。但由于例数不多 ,这一结果有待于进一步研究证实     

谷胱甘肽硫转移酶M1基因多态与肺癌易感性的关系

目的探讨谷胱甘肽硫转移酶M1（GSTM1）基因多态与支气管肺癌癌变的关系。方法采用回顾性“病例—对照”设计和限制性片段多态检测法（PCR—RFLP）,检测肺癌病例组103例和正常对照组138例的G卯Ml基因多态,以非条件性logistic回归模型分别对年龄、性别进行校正后计算比数比（OR）及95％可信区间（CI）。结果GSTM1的缺陷型基因（D）频率在对照组、肺癌组分别为44.2％和61．2％。logistic回归分析表明．GSTMl缺陷型（D）患肺癌的危险度升高2．09倍,差异有统计学意义。GSTM1（D）可显著增加鳞癌和小细胞癌的患病危险度。结论GSTM1（D）是患肺癌的危险因素,GSTM1（D）存在与吸烟有协同作用。     

Glutathione S-transferase A1 polymorphism as a risk factor for smoking-related type 2 diabetes among Japanese

Glutathione S-transferases protect cells against exogenous and endogenous oxidative stress. Type 2 diabetes is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This study investigated whether GSTA1*A/*B and GSTP1 Ile105Val polymorphisms could affect the risk for type 2 diabetes. A cross-sectional case-control analysis included 468 (326 men and 142 women) Japanese participants in a health screening program. The prevalence of type 2 diabetes was 11.3% (63 subjects: 52 male and 11 female). The frequency of GSTA1*B allele carriers was higher in diabetes than in non-diabetes, though the difference was not statistically significant (adjusted OR, 1.8; 95% CI, 0.9–3.4). The risk among the GSTA1*B allele carriers was significantly increased by current-smoking status (adjusted OR, 3.7; 95% CI, 1.1–12.7; vs. never-smoking non-carriers), whereas the smoking status was not an independent risk factor. The GSTP1 genotype alone or in combination with the smoking status did not affect the risk for diabetes. This is the first report to show that the GSTA1*B allele is a potential risk factor for smoking-related type 2 diabetes.     

Glutathione S-transferases M1 and T1 polymorphisms and arsenic content in hair and urine in two ethnic clans exposed to indoor combustion of high arsenic coal in Southwest Guizhou, China

A total of 2,402 cases of arsenic-related skin lesions (as of 2002) in a few villages of China’s Southwest Guizhou Autonomous Prefecture represent a unique case of endemic arseniasis related with indoor combustion of high arsenic coal. A significant difference of skin lesion prevalence was observed between two clans of different ethnicities (Hmong and Han) in one of the hyperendemic villages in this prefecture. This study was focused on a possible involvement of GST T1 and M1 polymorphisms in risk modulation of skin lesions and in the body burden of As in this unique case of As exposure. GST T1 and M1 polymorphisms were genotyped by an allele-specific PCR-based procedure. Total As contents in hair and urine samples as well as environmental samples of the homes of the two ethnic clans were analyzed. No significant deviations in the population frequencies of GST T1 and M1 0/0 genotypes or their combination were recorded between diagnosed skin lesion patients and asymptomatic individuals in both clans. Significantly higher As contents in hair and urine were observed in GSTM1 0/0 carriers, not in GSTT1 0/0 carriers. After stratified by ethnicity and gender, a statistically significant association of the GSTM1 0/0 genotype and higher As content in hair was only confirmed in the subgroups of ethnic Han clan members and all male villagers, not in ethnic Hmong clan members or in females. GST T1 and M1 homozygous deletions were not associated with an increased susceptibility to skin lesions in long-term exposure to indoor combustion of high As coal. The polymorphic status at the locus of GSTM1 might modulate individual’s body burden of total As in some Chinese ethnic groups.