Abstract
BackgroundN-acetyltransferase 2 plays a crucial role in the metabolism of a wide range of xenobiotics, including many drugs, carcinogens, and other chemicals in the human environment. The article presents for the first time data on the frequency of two important “slow” variants of NAT2 gene (NAT2*5, rs1801280 and NAT2*7, rs1799931), which significantly affect the rate of xenobiotics acetylation, among representatives of indigenous populations of Forest and Tundra Nenets in Northern Siberia. The aim of this study was to identify the frequencies of these variants and compare them with frequencies in other ethnic populations.ResultsNAT2*5 (T341C) genotyping revealed frequencies of 28,0% and 38,6% for Tundra and Forest Nenets, respectively. The frequencies of NAT2*7 (G857A) variant were 9,8% and 8,2% for Tundra and Forest Nenets, respectively. Polymorphic variants frequencies for Nenets are intermediate between those in populations of Europeans and Asians. These results can probably be explained by the presence of both European and Asian components in Nenets gene pools.ConclusionsThe results of this study expand the knowledge of NAT2 polymorphism in world populations. These data may also help assess the genetic predisposition of Nenets to multifactorial diseases associated with polymorphism in the NAT2 gene and, in general, contribute to the development of personalized medicine in reference to native people of Siberia.
Highlights
N-acetyltransferase 2 plays a crucial role in the metabolism of a wide range of xenobiotics, including many drugs, carcinogens, and other chemicals in the human environment
Foreign substances entering the body are metabolized by the enzymes of the xenobiotic biotransformation system (XBS)
As described above, the polymorphic variant NAT2*5 (341C) is found in the world populations with an average frequency of 30–50% among Europeans, 33–42% among Africans, and quite rarely among Asians
Summary
N-acetyltransferase 2 plays a crucial role in the metabolism of a wide range of xenobiotics, including many drugs, carcinogens, and other chemicals in the human environment. A person’s life expectancy and quality of life are determined by many factors, including heredity, lifestyle, physical activity, nutrition, stress, and the exposure to foreign substances (xenobiotics). These include exotoxins, mutagens and carcinogens in tobacco smoke, food, air, medicines, industrial and agricultural products [1,2,3]. Numerous studies have shown that the combination of adverse environmental factors with the inheritance of unfavorable polymorphic variants of genes, which include XBS genes, determines individual sensitivity to various toxins. Such sensitivity may contribute to the development of socially significant diseases in both adults and children. Resistance or hypersensitivity of an individual to a particular drug may lead to lack of therapeutic effect
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