Mishra Dhruva K, Kumar Anant, Srivastava Daya Shankar L, Mittal Rama D
Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow-226014, Uttar Pradesh, India.
Asian Pac J Cancer Prev. 2004 Oct-Dec;5(4):362-5.
Glutathione S-transferase (GST) enzymes are involved in detoxification of many potentially carcinogenic compounds. Homozygous deletions or null genotypes of GSTT1 and GSTM1 genes and an A to G substitution at nucleotide 313 in GSTP1 have been reported in different populations. Intra-ethnic as well as interethnic differences are known to exist in the frequencies of the above GST genes. The present study was therefore undertaken to determine the prevalence of GSTM1 and GSTT1null alleles, as well as the GSTP1 gene polymorphism, in 370 healthy individuals in a North Indian population. Genotyping of M1 and T1 was performed using a multiplex polymerase chain reaction and the GSTP1 polymorphism was determined by the polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of GSTM1 and GSTT1 null alleles in normal healthy individuals were observed to be 33.0% and 18.4% respectively. In 7.0% of individuals' concomitant lack of M1 and T1 genes were observed. For GSTP1, wild (Ile/Ile), heterozygous (Ile/Val) and mutant (Val/Val) genotypes were observed for 44.3%, 50.3% and 5.4% of individuals respectively. The prevalence of the M1 null allele is significantly lower than those documented for English, Turkish, Chinese, Caucasians, Japanese and white (Brazilian and American) populations. However, a significantly higher frequency for T1 null was reported in Chinese and Japanese population. Furthermore, Japanese and African American populations have exhibited significantly higher frequencies of wild and mutant P1 genotypes, respectively, than the Indian population. Thus, our results signify an impact of ethnicity and provide a basis for future epidemiological and clinical studies.
谷胱甘肽S-转移酶(GST)参与多种潜在致癌化合物的解毒过程。在不同人群中已报道了GSTT1和GSTM1基因的纯合缺失或无效基因型以及GSTP1基因第313位核苷酸由A到G的替换。已知上述GST基因的频率在种族内部以及种族之间存在差异。因此,本研究旨在确定北印度人群中370名健康个体的GSTM1和GSTT1无效等位基因的流行情况以及GSTP1基因多态性。使用多重聚合酶链反应对M1和T1进行基因分型,并通过聚合酶链反应/限制性片段长度多态性(PCR-RFLP)方法确定GSTP1多态性。正常健康个体中GSTM1和GSTT1无效等位基因的频率分别为33.0%和18.4%。在7.0%的个体中观察到同时缺乏M1和T1基因。对于GSTP1,野生型(Ile/Ile)、杂合型(Ile/Val)和突变型(Val/Val)基因型分别在44.3%、50.3%和5.4%的个体中观察到。M1无效等位基因的流行率显著低于英国、土耳其、中国、高加索、日本以及白人(巴西和美国)人群的报道。然而,中国和日本人群中T1无效等位基因的频率显著更高。此外,日本和非裔美国人群野生型和突变型P1基因型的频率分别比印度人群显著更高。因此,我们的结果表明种族的影响,并为未来的流行病学和临床研究提供了基础。