<i>GSTM1</i> and <i>GSTT1</i> polymorphisms in healthy volunteers – a worldwide systematic review

The <i>GSTM1</i> and <i>GSTT1</i> genes encode homonymous enzymes, which are responsible for the detoxification of several substances potentially harmful to the human body, such as air pollution, drugs, pesticides, and tobacco. However, some individuals may present a complete deletion of these genes and, consequently, an enzyme deficiency leading to an inadequate metabolism and, therefore, a higher susceptibility to some clinical conditions. Interethnic variations have also been described for both genes, making necessary the study of the deletion frequencies of <i>GSTM1</i> and <i>GSTT1</i> in different populations around the world. So, the aim of this study was to enable the synthesis and discussion of the main population differences of <i>GSTM1</i> and <i>GSTT1</i> polymorphisms in healthy volunteers. Searches were performed in the PubMed database, including 533 articles and 178,566 individuals in the analyses. We found an overrepresentation of European individuals and studies, and an underrepresentation of non-European ethnicities. Moreover, there are significant frequency differences among distinct ethnic groups: East Asians present the highest frequencies worldwide for <i>GSTM1</i> and <i>GSTT1</i> deletions, which could suggest higher disorders risk for this population; in contrast, Sub-Saharan Africans presented the lowest frequency of <i>GSTM1</i> worldwide, corroborating evolution inferences performed previously for other genes codifying metabolism enzymes. Also, admixture is a relevant component when analyzing frequency values for both genes, but further studies focusing on this subject are warranted.<i>GSTM1</i>与<i>GSTT1</i>基因可编码同名酶类，负责对多种对人体具有潜在危害的物质进行解毒代谢，包括空气污染、药物、农药及烟草成分。然而，部分个体可出现这两类基因的完全缺失，进而引发酶缺乏症，造成代谢功能不全，最终使该群体对某些临床病症的易感性升高。此外，已有研究证实这两类基因存在族间遗传差异，因此有必要针对全球不同人群开展<i>GSTM1</i>与<i>GSTT1</i>基因缺失频率的相关研究。本研究旨在系统汇总并探讨健康志愿者中<i>GSTM1</i>与<i>GSTT1</i>基因多态性的主要人群差异。研究团队在PubMed数据库中开展文献检索，最终纳入533篇相关文献，累计分析样本量达178566名个体。研究结果显示，欧洲人群及相关研究占比过高，而非欧洲族裔的相关研究则代表性不足。此外，不同族裔群体间的基因缺失频率存在显著差异：东亚人群的<i>GSTM1</i>与<i>GSTT1</i>基因缺失频率为全球最高，这提示该群体罹患相关疾病的风险更高；与之相反，撒哈拉以南非洲人群的<i>GSTM1</i>基因缺失频率为全球最低，这与此前针对其他代谢酶编码基因的进化生物学推论相符。此外，遗传混杂在分析两类基因的频率数据时是一项不可忽视的重要因素，但未来仍需开展聚焦该主题的深入研究。