Genetic polymorphisms of CYP2D6, CYP1A1, GSTM1 and p53 genes in a unique Siberian population of Tundra Nentsi

Abstract

The purpose of this study was to establish the frequencies of CYP2D6, CYP1A1, GSTM1 and p53 polymorphic genotypes in Tundra Nentsi, which comprises the small group of indigenous people belonging to Northern Mongoloids and Caucasians of Western Siberia. A total number of 102 Tundra Nentsi individuals and 96 Caucasians of Western Siberia were genotyped by means of polymerase chain reaction-based assays. Mutated alleles comprising CYP2D6*4, CYP1A1Val, GSTM1*0 and p53Pro were analysed along with the wild-type alleles. The results showed the intermedial position of CYP2D6*4 allele frequency in Tundra Nentsi, compared to Caucasians and Orientals (0.07 versus 0.2, P = 0.0003; 0.07 versus 0.003, P = 1 x 10(-6), respectively). Thus, our data indicate that the intermedial position of Tundra Nentsi between Orientals and Caucasians most likely shows the Caucasian ancestral origin of CYP2D6*4 allele. Comparative analysis of p53Pro allele frequency showed the pronounced ethnic differences with geographic gradient. Though the frequency of p53Pro allele ranged from 0.17 in Tundra Nentsi up to 0.3 in Caucasians of Western Siberia (P = 0.002), which is in agreement with the previously reported radial distribution of the known genetic markers. No differences were found in the CYP1A1Val allele distribution among Caucasians of Western Siberia and Caucasoid populations presented in other studies, whereas the frequency of Val allele in Nentsi was 1.5-fold higher (P = 0.076) compared to the Japanese group. It was found that the frequency of GSTM1 null genotype in Tundra Nentsi was only 39.8%. The frequency of GSTM1 null genotype in females was higher than in males (0.27 and 0.50, respectively) but that difference was not statistically significant. Comparative analyses of the distribution of putative markers towards cancer susceptibility, CYP1A1Val, GSTM1*0 and p53Pro alleles, have shown that the healthy Tundra Nentsi population (Northern Mongoloids) have a low number of p53Pro alleles and GSTM1*0/*0 genotypes and a high level of CYP1A1Val alleles. Further investigations of gene polymorphisms in isolated Northern native populations would be valuable in clarifying the origin of Northern natives. All this is important for comparative analyses of pharmacogenetic data in Mongoloid populations.

Polymorphisms of the GSTM1, GSTT1, and CYP2D6 xenobiotic biotransformation genes, which are possible risk markers of cancer in populations of indigenous ethnic groups and Russians of North Siberia

“…Frequencies of the CYP2D6*4 allele have intermediate values between those for Mongoloids of China and Russians of Siberia. A similar conclusion was made during the investigation of the sample of Tundra Nenets (102 individuals) (Duzhak et al, 2000). The frequency of CYP2D6*4 in studied sample of Russians of Siberia is consistent with the data obtained for the sample of Russians (N = 290) who live in the Cauca soid part of Russia (Voronezh oblast) (18.2%; p = 0.73) and in Estonia (14.4%; p = 0.35), as well as for the European German sample (20.7%; p = 0.15) (Sachse et al, 1997;Marandi et al, 1997;Gaikovitch et al, 2003).…”

“…According to the literature data, in the related (by language) to the Forest Nenets population of Sam burg Tundra Nenets, approximately the same fre quency of GSTM1 0/0 (39.8%; p = 0.71) was recorded in the sample of 102 practically healthy individuals (Duzhak et al, 2000). However, among Tundra Nenets with cancer or chromosome anomalies (N = 28), the frequency of the "null" GSTM1 0/0 genotype was (Duzhak et al, 2001). Thus, an association between the presence of the mutant "null" GSTM1 0/0 genotype and the risk of the development of cancer was demonstrated for the first time in Samoyedic ethnic groups.…”

“…In Forest Nenets, an unusually high fre quency of GSTM1 0/0 (approximately 35%) was found. According to the literature data, in the related (by language) to the Forest Nenets population of Sam burg Tundra Nenets, approximately the same fre quency of GSTM1 0/0 (39.8%; p = 0.71) was recorded in the sample of 102 practically healthy individuals (Duzhak et al, 2000). However, among Tundra Nenets with cancer or chromosome anomalies (N = 28), the frequency of the "null" GSTM1 0/0 genotype was (Duzhak et al, 2001).…”

Comparison of <em>CYP2C9</em>, <em>CYP2C19</em>, <em>CYP2D6</em>, <em>ABCB1</em>, and <em>SLCO1B1</em> gene-polymorphism frequency in Russian and Nanai populations

“…Tatars and Bashkirs, ethnic groups living in the European part of Russia, have frequencies of CYP2C9*2 of 5.1% and 6%, CYP2C9*3 of 5.4% and 6.2%, and CYP2D6*4 of 9.5% and 7.1%, respectively 16,17. The Nenets have a frequency of CYP2D6*4 of 7.3% 18. However, we do not have any pharmacogenetic data for many ethnic groups in Russia, and we do not have such data for the Nanai people.…”

Pharmacogenomics of Xenobiotic Metabolizing Enzymes in South American Populations

“…These polymorphisms are not common among Caucasians or Africans but are more frequent in Asians [Hayashi et al 1991;Shields et al 1993;Cascorbi et al 1996;Garte et al 1996;Masimirembwa et al 1998]. The highest frequencies found for these alleles in non-Amerindian populations are 0.33 for *2A in Japanese [Aynacioglu et al 1998] and 0.35 for *2C in Siberians [Duzhak et al 2000] which are still much lower than those observed for the Amerindians. The frequency of the *2C allele has also been investigated in different Brazilian cities as shown in Table 1.…”