Cytochrome P450 2A13 3375C>T gene polymorphism in a Turkish population

Abstract

Background and Aims: The polymorphisms in genes encoding xenobiotic-metabolizing enzymes may change the metabolic activation of various xenobiotics and therefore may affect individuals’ susceptibility to xenobiotics-induced toxic effects. Cytochrome P450 2A13 (CYP2A13) is an important CYP enzyme predominantly expressed in the human respiratory tract. CYP2A13 metabolizes the xenobiotics and bioactivation of several carcinogens. The present study aimed to determine the allele and genotype frequencies of CYP2A13 3375C>T polymorphism in a Turkish population and also to compare the obtained results with those of various populations. Methods: CYP2A13 3375C>T polymorphism was determined in 93 healthy Turkish individuals using the polymerase chain reaction-restriction fragment length method. Results: The frequencies of CC, CT and TT genotypes were 89.2%, 9.7% and 1.1%, respectively. The frequencies of C and T alleles were 94.1% and 5.9%, respectively. The genotype frequencies did not deviate from the Hardy-Weinberg equilibrium. Significant differences were observed when comparing the results found with those of various populations, especially those of populations with black ancestry (excluding Tunisian). Conclusion: This study can provide valuable data for further studies investigating the role of this polymorphism concerning the susceptibility to xenobiotics-induced toxic effects, including cancer, and may be used as a control group for such studies and also may contribute to toxicogenetic and epidemiological studies.

Keywords

• CYP2A13 3375C>T
• genetic polymorphism
• Arg257Cys
• Turkish population

References

1. • Alzahrani, A. M., & Rajendran, P. (2020). The multifarious link between cytochrome P450s and cancer. Oxidative Medicine and Cellular Longevity, 2020:3028387.
2. • Cauffiez, C., Pottier, N., Tournel, G., Lo-Guidice, J. M., Allorge, D., Chevalier, D., Migot-Nabias, F., Kenani, A., & Broly, F. (2005). CYP2A13 genetic polymorphism in French Caucasian, Gabonese and Tunisian populations. Xenobiotica, 35(7), 661−669.
3. • Cheng, X. Y., Chen, G. L., Zhang, W. X., Zhou, G., Wang, D., & Zhou, H. H. (2004). Arg257Cys polymorphism of CYP2A13 in a Chinese population. Clinica Chimica Acta, 343(1-2), 213−216.
4. • D‘Agostino, J., Zhang, X., Wu, H., Ling, G., Wang, S., Zhang, Q.Y., Liu, F., & Ding, X. (2008). Characterization of CYP2A13*2, a variant cytochrome P450 allele previously found to be associated with decreased incidences of lung adenocarcinoma in smokers. Drug Metabolism and Disposition, 36(11), 2316−2323.
5. • Elfaki, I., Mir, R., Almutairi, F. M., & Duhier, F. M. A. (2018). Cytochrome P450: Polymorphisms and Roles in Cancer, Diabetes and Atherosclerosis. Asian Pacific Journal of Cancer Prevention, 19(8), 2057−2070.
6. • Fujieda, M., Yamazaki, H., Kiyotani, K., Muroi, A., Kunitoh, H., Dosaka- Akita, H., Sawamura, Y., & Kamataki, T. (2003). Eighteen novel polymorphisms of the CYP2A13 gene in Japanese. Drug Metabolism and Pharmacokinetics, 18(1), 86−90.
7. • Fukami, T., Nakajima, M., Matsumoto, I., Zen, Y., Oda, M., & Yokoi, T. (2010). Immunohistochemical analysis of CYP2A13 in various types of human lung cancers. Cancer Science, 101(4), 1024−1028.
8. • Fukami, T., Nakajima, M., Sakai, H., Katoh, M., & Yokoi, T. (2007). CYP2A13 metabolizes the substrates of human CYP1A2, phenacetin, and theophylline. Drug Metabolism and Disposition, 35(3), 335–339.

9. • Herr, D., Bettendorf, H., Denschlag, D., Keck, C., & Pietrowski, D. (2006). Cytochrome P2A13 and P1A1 gene polymorphisms are associated with the occurrence of uterine leiomyoma. Archives of Gynecology and Obstetrics, 274(6), 367−371.
10. • http-1: https://www.pharmvar.org/gene/CYP2A13. Accessed 10.04.2020. • http-2: https://www.internationalgenome.org/1000-genomesbrowsers/. Accessed 03.04.2020.
11. • Jiang, J. H., Jia, W. H., Chen, H. K., Feng, B. J., Qin, H. D., Pan, Z. G., Shen, G. P., Huang, L. X., Feng, Q. S., Chen, L. Z., Lin, D. X., & Zeng, Y. X. (2004). Genetic polymorphisms of CYP2A13 and its relationship to nasopharyngeal carcinoma in the Cantonese population. Journal of Translational Medicine, 2(1), 24.
12. • Kim, V., Yeom, S., Lee, Y., Park, H. G., Cho, M. A., Kim, H., & Kim, D. (2018). In vitro functional analysis of human cytochrome P450 2A13 genetic variants: P450 2A13*2, *3, *4, and *10. Journal of Toxicology and Environmental Health. Part A, 81(12), 493−501.
13. • Korytina, G., Kochetova, O., Akhmadishina, L., Viktorova, E., & Victorova, T. (2012). Polymorphisms of cytochrome p450 genes in three ethnic groups from Russia. Balkan Medical Journal, 29(3), 252−260.
14. • Kumondai, M., Hosono, H., Orikasa, K., Arai, Y., Arai, T., Sugimura, H., Ozono, S., Sugiyama, T., Takayama, T., Sasaki, T., Hirasawa, N., & Hiratsuka, M. (2016). CYP2A13 Genetic Polymorphisms in Relation to the Risk of Bladder Cancer in Japanese Smokers. Biological & Pharmaceutical Bulletin, 39(10), 1683−1686.
15. • Schlicht, K. E., Michno, N., Smith, B. D., Scott, E. E., & Murphy, S. E. (2007). Functional characterization of CYP2A13 polymorphisms. Xenobiotica, 37(12), 1439−1449.
16. • Sharma, R., Ahuja, M., Panda, N., & Khullar, M. (2010). Polymorphisms in CYP2A13 and UGT1A7 genes and head and neck cancer susceptibility in North Indians. Oral Diseases, 16(8), 760−768.
17. • Song, D. K., Xing, D. L., Zhang, L. R., Li, Z. X., Liu, J., & Qiao, B. P. (2009). Association of NAT2, GSTM1, GSTT1, CYP2A6, and CYP2A13 gene polymorphisms with susceptibility and clinicopathologic characteristics of bladder cancer in Central China. Cancer Detection and Prevention, 32(5-6), 416−423.
18. • Su, T., Bao, Z., Zhang, Q. Y., Smith, T. J., Hong, J. Y., & Ding, X. (2000). Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone. Cancer Research, 60(18), 5074−5079.
19. • Tamaki, Y., Honda, M., Muroi, Y., Arai, T., Sugimura, H., Matsubara, Y., Kanno, S., Ishikawa, M., Hirasawa, N., & Hiratsuka, M. (2011a) Novel single nucleotide polymorphism of the CYP2A13 gene in Japanese individuals. Drug Metabolism and Pharmacokinetics, 26(5), 544–547.
20. • Tamaki, Y., Arai, T., Sugimura, H., Sasaki, T., Honda, M., Muroi, Y., Matsubara, Y., Kanno, S., Ishikawa, M., Hirasawa, N., & Hiratsuka, M. (2011b) Association between cancer risk and drug-metabolizing enzyme gene (CYP2A6, CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1) polymorphisms in cases of lung cancer in Japan. Drug Metabolism and Pharmacokinetics, 26(5), 516−522.
21. • Timofeeva, M. N., Kropp, S., Sauter, W., Beckmann, L., Rosenberger, A., Illig, T., Jäger, B., Mittelstrass, K., Dienemann, H.; LUCY-Consortium, Bartsch, H., Bickeböller, H., Chang-Claude, J. C., Risch, A., & Wichmann, H. E. (2009). CYP450 polymorphisms as risk factors for early-onset lung cancer: gender-specific differences. Carcinogenesis, 30(7), 1161−1169.
22. • Uckun Sahinogullari, Z. (2020). Genetic polymorphism of CYP2C8* 4 in a healthy Turkish population. Medicine Science, 9(2), 314−319.
23. • Wang, S. L., He, X. Y., Shen, J., Wang, J. S., & Hong, J. Y. (2006). The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant. Toxicological Sciences, 94(1), 38−45.
24. • Wang, H., Tan, W., Hao, B., Miao, X., Zhou, G., He, F., & Lin, D. (2003). Substantial reduction in risk of lung adenocarcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco-specific carcinogen NNK. Cancer Research, 63(22), 8057–8061.
25. • Zhang, X., Su, T., Zhang, Q. Y., Gu, J., Caggana, M., Li, H., & Ding, X. (2002). Genetic polymorphisms of the human CYP2A13 gene: identification of single-nucleotide polymorphisms and functional characterization of an Arg257Cys variant. Journal of Pharmacology and Experimental Therapeutics, 302(2), 416−423.
26. • Zhou, S. F., Liu, J. P., & Chowbay, B. (2009). Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metabolism Reviews, 41(2), 89−295.