The ILE462VAL polymorphism of the cytochrome P450 CYP1A1 gene in the Tundra Nenets of the Yamalo-Nenets Autonomous Okrug, Nganasans of the Taimyr Peninsula, and Russians of Siberia

Abstract

This paper concerns a polymorphism of the cytochrome Р450 CYP1A1 gene, the CYP1A1*2C variant (Ile462Val, rs1048943). This substitution results in the doubling of enzyme activity, which leads to the accumulation of active intermediates and increases the risk of DNA mutations and chemically induced carcinogenesis. It has been demonstrated that the 462Val allele may be a risk factor in some oncological and other multifactorial diseases. This study was carried out on Tundra Nenets of the Yamalo-Nenets Autonomous Okrug (n = 271), Nganasans in the Taimyr Peninsula (n = 186), and Russians in North Siberia (n = 267). The cohorts did not include descendants of mixed marriages. Genotyping was performed using real-time PCR with competitive TaqMan allele-specific probes. The frequency of the 462Val allele in the Tundra Nenets cohort was 23.8% (95% CI 20.4–27.6%), which corresponds to the frequency range found in East Asian populations and is higher than the values typical of Caucasoid populations. The 462Val allele frequency in the Russian cohort was 5.8% (95% CI 4.1–8.1%), which corresponds to the frequency range of Caucasoid populations. The 462Val allele frequency in the Nganasans cohort was 39.0% (95% CI 34.2–44.0%), which is higher than the frequencies found in the European, Asian and African populations. Frequencies of the 462Val variant close to that in Nganasans have been observed in Greenland’s Inuits, Native Americans, and Southern Chinese. Thus, in the populations of Tundra Nenets and Nganasans the CYP1A1 462Val allele occurs at a high frequency, greater than those typical of Caucasoid populations. A high-frequency occurrence of the 462Val allele may be indicative of a population-wide risk of diseases influenced by this genetic polymorphism, especially when the traditional mainstays are gone or previously unknown ecotoxicants appear in the areas.