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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

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Russian Journal of Genetics: Applied Research

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.

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References

  • Androutsopoulos, V.P., Tsatsakis, A.M., and Spandidos, D.A., Cytochrome p450 CYP1A1: Wider roles in cancer progression and prevention, BMC Cancer, 2009, vol. 9, pp. 187–203. doi 10.1186/1471-2407-9-187

    Article  PubMed  PubMed Central  Google Scholar 

  • Baranov, V.S., Baranova, E.B., and Ivashchenko, T.E., Genom cheloveka i “geny predraspolozhennosti” (Vvedenie v prediktivnuyu meditsinu) (Human Genome and Susceptibility Genes (Introduction to Predictive Medicine)), St. Petersburg: Intermedika, 2000.

    Google Scholar 

  • Bjerregaard, P., Dewailly, E., Ayotte, P., Pars, T., Ferron, L., and Mulvad, G., Exposure of Inuit in Greenland to organochlorines through the marine diet, J. Toxicol. Environ. Heal. A, 2001, vol. 62, no. 2, pp. 69–81. doi 10.1080/009841001455490

    Article  CAS  Google Scholar 

  • Boyapati, S.M., Shu, X.O., Gao, Y.T., Cai, Q., Jin, F., and Zheng, W., Polymorphisms in CYP1A1 and breast carcinoma risk in a population-based case-control study of Chinese women, Cancer, 2005, vol. 103, no. 10, pp. 2228–2235. doi doi 10.1002/cncr.21056

    Article  CAS  PubMed  Google Scholar 

  • Butkiewicz, D., Cole, K.J., Phillips, D.H., Harris, C.C., and Chorazy, M., GSTMI,GSTP1,CYP1A1,and CYP2D6 polymorphisms in lung cancer patients from an environmentally polluted region of Poland: Correlation with lung DNA adduct levels, Eur. J. Cancer Prev., 1999, vol. 8, no. 4, pp. 315–324. doi 10.1097/00008469-199908000-00008

    Article  CAS  PubMed  Google Scholar 

  • Chen, S., Xue, K., Xu, L., Ma, G., and Wu, J., Polymorphisms of the CYP1A1 and GSTM1 genes in relation to individual susceptibility to lung carcinoma in Chinese population, Mutat. Res. Mutat. Res. Genomics, 2001, vol. 458, nos. 1–2, pp. 41–47. doi 10.1016/S1383-5726(01)00011-5

    Article  CAS  Google Scholar 

  • Chen, J., Cheng, M., Li, Y., and Jiang, C., Relationship between CYP1A1 genetic polymorphisms and renal cancer in China, Asian Pac. J. Cancer Prev., 2011, vol. 12, no. 9, pp. 2163–2166. 2008.00971 doi 10.3724/SP.J.1008

    PubMed  Google Scholar 

  • Derbeneva, O.A., Starikovskaya, E.B., Volodko, N.V., Wallace, D.C., and Sukernik, R.I., Mitochondrial DNA variation in the Kets and Nganasans and its implications for the initial peopling of Northern Eurasia, Russ. J. Genet., 2002, vol. 38, no. 11, pp. 1316–1321.

    Article  CAS  Google Scholar 

  • Dolgikh, B.O., Origin Nganasans, in Tr. In-Ta etnografii (Proceedings of the Ethnography Institute), 1952, vol. 18, pp. 5–87.

    Google Scholar 

  • Duzhak, T.G., Gutkina, N.I., Mitrofanov, D.V., Afanas’eva, O.A., Lyakhovich, V.V., Posukh, O.L., Kryukov, Yu.A., and Osipova, L.P., The study of polymorphisms of genes CYP1A1 and CYP2D6 in the populations of Tundra Nenets and Caucasians of Western Siberia, Genetika (Moscow), 1998, vol. 34, no. 11, pp. 1555–1558.

    CAS  Google Scholar 

  • Gallegos-Arreola, M.P., Batista-González, C.M., Delgado-Lamas, J.L., Figuera, L.E., Puebla-Pérez, A.M., Arnaud-López, L., Peralta-Leal, V., Ramírez-Jirano, L.J., and Zúñiga-González, G.M., Cytochrome P4501A1 polymorphism is associated with susceptibility to acute lymphoblastic leukemia in adult Mexican patients, Blood Cells Mol. Dis., 2004, vol. 33, no. 3, pp. 326–329. doi 10.1016/j.bcmd.2004.07.002

    Article  CAS  PubMed  Google Scholar 

  • Garte, S., Gaspari, L., Alexandrie, A.-K., Ambrosone, C., Autrup, H., Autrup, J.L., Baranova, H., Bathum, L., Benhamou, S., Boffetta, P., Bouchardy, C., Breskvar, K., Brockmoller, J., Cascorbi, I., Clapper, M.L., et al., Metabolic gene polymorphism frequencies in control populations, Cancer Epidemiol. Biomarkers Prev., 2001, vol. 10, no. 12, pp. 1239–1248.

    CAS  PubMed  Google Scholar 

  • Ghisari, M.E., Polimorphisms in phase I and phase II genes and breast cancer risk and relations to persistent organic pollutant exposure: A case-control study in Inuit women, Environ. Health, 2014, vol 13, no. 1, p. 19. doi 10.1186/1476-069x-13-19

    Article  PubMed  PubMed Central  Google Scholar 

  • Ghisari, M., Long, M., and Bonefeld-Jorgensen, E.C., Genetic polymorphisms in CYP1A1,CYP1B1,and COMT genes in Greenlandic Inuit and Europeans, Int. J. Circumpolar Health, 2013, vol. 72. http://www.circumpolarhealthjournal. net/index.php/ijch/article/view/21113. Accessed July 29, 2015. doi 10.3402/ijch.v72i0.21113

  • Gichev, Yu.P., Zagryaznenie okruzhayushchei sredy i zdorov’e cheloveka (Contamination of the Environment and Human Health), Novosibirsk: SO RAMN, 2002.

    Google Scholar 

  • Goltsova, T.V., Osipova, L.P., Zhadanov, S.I., and Villems, R., The effect of marriage migration on the genetic structure of the Taimyr Nganasan population: Genealogical analysis inferred from mtDNA markers, Russ. J. Genet., 2005, vol. 41, no. 7, pp. 779–788.

    Article  CAS  Google Scholar 

  • Gulyaeva, L.F. and Rais, R.Kh., Biologicheskie effekty toksicheskikh soedinenii (Biological Effects of Toxic Compounds), Novosibirsk: NGU, 2005.

    Google Scholar 

  • Hahn, M., Hagedorn, G., Kuhlisch, E., Schackert, H.K., and Eckelt, U., Genetic polymorphisms of drug-metabolizing enzymes and susceptibility to oral cavity cancer, Oral Oncol., 2002, vol. 38, no. 5, pp. 486–490. doi 10.1016/S1368-8375(01)00086-0

    Article  CAS  PubMed  Google Scholar 

  • Hasler, J.A., Estabrook, R., Murray, M., Pikuleva, I., Waterman, M., Capdevila, J., Holla, V., Helvig, C., Falck, J.R., Farrell, G., Kaminsky, L.S., Spivack, S.D., Boitier, E., and Beaune, F., Human cytochromes p450, Mol. Aspects Med., 1999, vol. 20, nos. 1–2, pp. 1–137. doi 10.1016/S0098-2997(99)00005-9

    Article  CAS  Google Scholar 

  • Hung, R.J., Boffetta, P., Brockmoller, J., Butkiewicz, D., Cascorbi, I., Clapper, M.L., Garte, S., Haugen, A., Hirvonen, A., Anttila, S., Kalina, I., Le Marchand, L., London, S.J., Rannug, A., Romkes, M., et al., CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: A pooled analysis, Carcinogenesis, 2003, vol. 24, no. 5, pp. 875–882. doi 10.1093/carcin/bgg026

    Article  CAS  PubMed  Google Scholar 

  • Ivaschenko, T.E., Shved, N.Yu., Kramareva, N.L., Aylamazian, E.K., and Baranov, V.S., Analysis of polymorphic alleles of the genes encoding the Phase 1 and 2 detoxication enzymes in patients with endometriosis, Russ. J. Genet., 2003, vol. 39, no. 4, pp. 427–430.

    Article  CAS  Google Scholar 

  • Izmailov, A.A., Pavlov, V.N., Izmailova, S.M., Mustafin, A.T., Urmantsev, M.F., Alekseev, A.V., Zagitov, A.R., Viktorova, T.V., and Nogmanova, V.A., Molecular genetic markers of prognosis in superficial bladder cancer, Med. Vestn. Bashkortostana, 2011, vol. 6, no. 5, pp. 47–51.

    Google Scholar 

  • Joseph, T., Kusumakumary, P., Chacko, P., Abraham, A., and Radhakrishna Pillai, M., Genetic polymorphism of CYP1A1, CYP2D6, GSTM1, and GSTT1 and susceptibility to acute lymphoblastic leukaemia in Indian children, Pediatr. Blood Cancer, 2004, vol. 43, no. 5, pp. 560–567. doi 10.1002/pbc.20167

    Google Scholar 

  • Karafet, T.M., Posukh, O.L., and Osipova, L.P., Population genetic studies of indigenous inhabitants of the Siberian North, Sib. Ekol. Zh., 1994, vol. 1, no. 2, pp. 113–127.

    Google Scholar 

  • Kochetova, O.V., Korytina, G.F., Akhmadishina, L.Z., Iskhakova, G.M., and Viktorova, T.V., Analysis of the cytochrome P450 1A1 (CYP1A1) gene polymorphism in the ethnic groups of the republic of Bashkortostan, Russ. J. Genet., 2008, vol. 44, no. 12, pp. 1454–1460.

    Article  CAS  Google Scholar 

  • Korytina, G.F., Yanbaeva, D.G., and Viktorova, T.V., Polymorphisms of the cytochrome P450 (CYP1A1, CYP2E1) and microsomal epoxide hydrolase (mEPHX) genes in cystic fibrosis and chronic respiratory disease, Mol. Biol. (Moscow), 2003, vol. 37, no. 5, pp. 663–670.

    CAS  Google Scholar 

  • Li, Y., Millikan, R.C., Bell, D.A., Cui, L., Tse, C.K., Newman, B., and Conway, K., Polychlorinated biphenyls, cytochrome P450 1A1 (CYP1A1) polymorphisms, and breast cancer risk among african american women and white women in North Carolina: A population based case-control study, Breast. Cancer Res., 2004, vol. 7, no. 1, pp. 12–18. doi 10.1186/bcr941

    Google Scholar 

  • London, S.J., Yuan, J.-M., Coetzee, G.A., Gao, Y.T., Ross, R.K., and Yu, M.C., CYP1A1 I462V genetic polymorphism and lung cancer risk in a cohort of men in Shanghai, China, Cancer Epidemiol. Biomarkers Prev., 2000, vol. 9, no. 9, pp. 987–991.

    CAS  PubMed  Google Scholar 

  • Lyakhovich, V.V., Vavilin, V.A., Makarova, S.I., and Grishanova, A.Yu., Ecogenetic aspect of polyfactorial diseases, Inf. Vestn. VOGiS, 2006, vol. 10, no. 3, pp. 514–519.

    Google Scholar 

  • Marques, C.F.S., Koifman, S., Koifman, R.J., Boffetta, P., Brennan, P., and Hatagima, A., Influence of CYP1A1, CYP2E1, GSTM3 and NAT2 genetic polymorphisms in oral cancer susceptibility: Results from a case-control study in Rio de Janeiro, Oral Oncol., 2006, vol. 42, no. 6, pp. 632–637. doi 10.1016/j.oraloncology.2005.11.003

    Article  CAS  PubMed  Google Scholar 

  • Minina, V.I., Druzhinin, V.G., Glushkov, A.N., Golovina, T.A., Apal’ko, S.V., Volkov, A.N., Akhmat’yanova, V.R., Lunina, A.A., and Larionov, A.V., Genotoxic effects of complex influence of radon and heavy metals, depending on gene polymorphisms in enzymes of the monooxygenase system, Ekol. Genet., 2009, vol. 7, no. 3, pp. 53–60.

    CAS  Google Scholar 

  • Nakachi, K., Imai, K., Hayashi, S., and Kawajiri, K., Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population, Cancer Res., 1993, vol. 53, no. 13, pp. 2994–2999. doi 10.1016/0169-5002(94)90751-x

    CAS  PubMed  Google Scholar 

  • Nebert, D.W. and Dalton, T.P., The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis, Nat. Rev. Cancer, 2006, vol. 6, no. 12, pp. 947–960. doi 10.1038/nrc2015

    Article  CAS  PubMed  Google Scholar 

  • Osipova, L.P. and Sukernik, R.I., Immunoglobulin allotypes in aboriginal populations of the Taimir Peninsula, J. Immunogenet., 1983, vol. 10, no. 1, pp. 11–16. doi 10.1111/j.1744-313X.1983.tb01011.x

    Article  CAS  PubMed  Google Scholar 

  • Osipova, L.P., Genetic markers of immunoglobulins (system Gm) for the evaluation of migration and cross-breeding in human populations in Northern Siberia, Sib. Ekol. Zh., 1994, vol. 1, no. 2, pp. 129–140.

    Google Scholar 

  • Osipova, L.P., Posukh, O.L., Ivakin, E.A., Kryukov, Yu.A., and Karafet, T.M., The gene pool of indigenous inhabitants of Samburg Tundra, Genetika (Moscow), 1996, vol. 32, no. 6, pp. 830–836.

    CAS  Google Scholar 

  • Razmkhah, F., Pazhakh, V., Zaker, F., Atashrazm, F., and Sheikhi, M., Frequency of CYP1A1*2C polymorphism in patients with leukemia in the Iranian population, Lab. Med., 2011, vol. 42, no. 4, pp. 220–223. doi 10.1309/LM337JWOSVNEHPUI

    Article  Google Scholar 

  • Rendic, S. and Guengerich, F.P., Summary of information on the effects of ionizing and non-ionizing radiation on cytochrome P450 and other drug metabolizing enzymes and transporters, Curr. Drug Metab., 2012, vol. 13, no. 6, pp. 787–814. doi 10.2174/138920012800840356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sam, S.S., Thomas, V., Reddy, K.S., Surianarayanan, G., and Chandrasekaran, A., CYP1A1 polymorphisms and the risk of upper aerodigestive tract cancers in an Indian population, Head Neck, 2008, vol. 30, no. 12, pp. 1566–1574. doi 10.1002/hed.20897

    Article  PubMed  Google Scholar 

  • Sambrook, J., Fritsch, E.F., and Maniatis, T., Molecular Cloning. A Laboratory Manual, New York: Cold Spring Harbor Laboratory, 1989.

    Google Scholar 

  • Saprin, A.N., Enzymes of metabolism and detoxification of xenobiotics, Usp. Biol. Khim., 1991, vol. 32, pp. 146–172.

    Google Scholar 

  • Sevost’yanova, N.V., Nekrasova, A.M., Koshel’, A.P., Dmitrieva, A.I., Martov, S.I., Klokov, S.S., and Rakitin, S.S., Polymorphism of DNA excision repair genes and genes of xenobiotic biotransformation enzymes in gastric cancer patients, Yakutsk. Med. Zh., 2009, vol. 2, no. 26, pp. 111–113.

    Google Scholar 

  • Shimada, T. and Fujii-Kuriyama, Y., Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and 1B1, Cancer Sci., 2004, vol. 95, no. 1, pp. 1–6. doi 10.1111/j.1349-7006.2004.tb03162.x

    Article  CAS  PubMed  Google Scholar 

  • Simchenko, Yu.B., Kul’tura okhotnikov na olenei Severnoi Evrazii (Culture of Deer Hunters in North Eurasia), Moscow: Nauka, 1976.

    Google Scholar 

  • Sukernik, R.I., Gol’tsova, T.V., Karafet, T.M., Osipova, L.P., and Galaktionov, O.K., Genetic structure of an isolated group of indigenous population of Northern Siberia, Nganasans (Tavgii) Taimyr. Part I. The history of the formation, erythrocyte and serum blood systems, isoenzymes, Genetika (Moscow), 1977, vol. 13, no. 9, pp. 1653–1661.

    CAS  Google Scholar 

  • Sukernik, R.I., Karaphet, T.M., and Osipova, L.P., Distribution of blood groups, serum markers and red cell enzymes in two human populations from Northern Siberia, Hum. Hered., 1978, vol. 28, no. 5, pp. 321–327. doi 10.1159/000152973

    Article  CAS  PubMed  Google Scholar 

  • Taspinar, M., Aydos, S.E., Comez, O., Elhan, A.H., Karabulut, H.G., and Sunguroglu, A., CYP1A1, GSTs gene polymorphisms and risk of chronic myeloid leukaemia, Swiss Med. Wkly., 2008, vol. 138, nos. 1–2, pp. 12–17. 2008/01/smw12036

    CAS  PubMed  Google Scholar 

  • The 1000 Genomes Project Consortium, An integrated map of genetic variation from 1092 human genomes, Nature, 2012, vol. 491, no. 7422, pp. 56–65. doi 10.1038/nature11632

  • Wilson, E.B., Probable inference, the law of succession, and statistical inference, J. Am. Stat. Assoc., 1927, vol. 22, no. 158, pp. 209–212. doi 10.2307/2276774

    Article  Google Scholar 

  • Xue, K., Xu, L., Chen, S., Ma, G., and Wu, J., Polymorphisms of the CYP1a1 and GSTm1 genes in relation to individual susceptibility to lung carcinoma in Chinese population, Mutat. Res., 2001, vol. 458, nos. 1–2, pp. 41–47. doi 10.1016/S1383-5726(01)00011-5

    PubMed  Google Scholar 

  • Zhang, Z., Pelletier, R.D., Wong, Y.N., Sugawara, M., Zhao, N., and Littlefield, B.A., Preferential inducibility of CYP1A1 and CYP1A2 by TCDD: Differential regulation in primary human hepatocytes versus transformed human cells, Biochem. Bioph. Res. Co., 2006, vol. 341, no. 2, pp. 399–407.

    Article  CAS  Google Scholar 

  • Zhuchenko, N.A., Umnova, N.V., Rumak, V.S., Revazova, Yu.A., Sidorova, I.E., Khripach, L.V., Lazarenko, D.Yu., and Sofronov, G.A., Congenital morphogenetic variations and genetic polymorphisms of the xenobiotic detoxification system in children from dioxin-contaminated areas of South Vietnam, Vestn. Ross. Akad. Med. Nauk, 2006, vol. 7, pp. 3–10.

    Google Scholar 

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia

    R. P. Tiis, L. P. Osipova, T. V. Churkina, L. E. Tabikhanova & D. V. Lichman

  2. Novosibirsk State University, Novosibirsk, Russia

    L. P. Osipova, D. V. Lichman, E. N. Voronina & M. L. Filipenko

  3. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia

    E. N. Voronina & M. L. Filipenko

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Original Russian Text © R.P. Tiis, L.P. Osipova, T.V. Churkina, L.E. Tabikhanova, D.V. Lichman, E.N. Voronina, M.L. Filipenko, 2016, published in Vavilovskii Zhurnal Genetiki i Selektsii, 2016, Vol. 20, No. 1, pp. 16–22.

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Tiis, R.P., Osipova, L.P., Churkina, T.V. et al. 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. Russ J Genet Appl Res 6, 864–870 (2016). https://doi.org/10.1134/S2079059716070133

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