High Frequency of CYP2A6*4, CYP2A6*7, and CYP2A6*9 Alleles Detected Among Patients with Type 2 Diabetic: Genetic Study in The Private Hospital in Yogyakarta

Christine Patramurti(1*), Dita Maria Virginia(2), Fenty Fenty(3), Christianus Heru Setiawan(4), Jeffry Julianus(5), Phebe Hendra(6), Nicholas Adi Perdana Susanto(7),

(1) Faculty of Pharmacy, Universitas Sanata Dharma
(2) Faculty of Pharmacy, Universitas Sanata Dharma
(3) Faculty of Pharmacy, Universitas Sanata Dharma
(4) Faculty of Pharmacy, Universitas Sanata Dharma
(5) Faculty of Pharmacy, Universitas Sanata Dharma
(6) Faculty of Pharmacy, Universitas Sanata Dharma
(7) Bethesda Lempuyangwangi Hospital, Yogyakarta, Indonesia
(*) Corresponding Author

Abstract


Smoking is a risk factor for type 2 diabetic (T2DM), since the nicotine in cigarettes can cause insulin resistance and increase lipolysis. Both of these can worsen the condition of patients with T2DM and increase treatment failure. Nicotine is metabolized to cotinine by the CYP2A6 enzyme encoded by the CYP2A6 gene. This gene is highly polymorphic, with several inactive alleles, which are CYP2A6 *4, CYP2A6 *7, and CYP2A6 *9. Someone who has an inactive gene will experience being a slow or poor metabolizer. Therefore, the nicotine metabolism will decrease, nicotine blood levels will increase, causing therapy failure among patients with T2DM. This study aims to determine the distribution of CYP2A6*4, CYP2A6*7, and CYP2A6*9 among patients with T2DM who have been routinely treated using oral antidiabetics. We also investigated whether HbA1c levels is a predictor for the success of the treatment. This observational study was conducted with a cross-sectional design. Polymerase chain reaction was used to analyze the three inactive alleles with specific primers. Based on our study, there is a high frequency of the inactive alleles, i.e., CYP2A6*4, CYP2A6*7, and CYP2A6*9, among the patients with T2DM. The presence of these inactive alleles will worsen and reduce the effectiveness of the therapy. Smoking cessation programs are needed to increase the effectiveness of the anti-diabetic therapy.

Keywords


Inactive allele; CYP2A6; smoking; T2DM patients

Full Text:

PDF

References


Alva, M.L., Hoerger, T.J., Zhang, P., Gregg, E.W., 2017. Identifying risk for type 2 diabetic in different age cohorts: does one size fit all ? Diabetic Research and Care, 5(1), 1–7.

Ando, M., Hamajima, N., Ariyoshi, N., Kamataki, T., Matsuo, K., Ohno, Y., 2003. Association of CYP2A6 gene deletion with cigarette smoking status in Japanese adults. Journal of epidemiology / Japan Epidemiological Association, 13(3), 176–181.

Bajaj, M., 2012. Nicotine and insulin resistance: when the smoke clears. Diabetic, 61(12), 3078–3080.

Berenson, G.S.B., Nguyen, Q.M., Xu, J.H., Chen, W., and Srinivasan, S.R., 2012. Correlates of age onset of type 2 diabetic among relatively young black and white adults in a community. Diabetic Care, 35, 1341–1246.

Binh, T.Q., Nhung, B.T., 2015. Prevalence and risk factors of type 2 diabetic in middle-aged women in Northern Vietnam. Int J Diabetic Dev Ctries, 36(2), 150-157.

Borowitz, J.L., Isom, G.E., 2008. Nicotine and type 2 diabetic. Toxicological Sciences, 103(2), 225–227.

Bösenberg, L.H., Van Zyl, D.G., 2008. The mechanism of action of oral antidiabetic drugs: A review of recent literature. Journal of Endocrinology, Metabolism and Diabetic of South Africa, 13(3), 80–89.

Buell, C., Kermah, D., Davidson, M.B., 2007. Utility of A1C for diabetic screening in the 1999 2004 NHANES population. Diabetic Care, 30(9), 2233–2235.

C. Patramurti, E.J. Candaya, S.F. Kiatarto, A.K.K., 2019. Polimorfisme Gen Sitokrom P450 2A6 Alel *1, *4, *7 dan *9 pada Subyek Uji Perokok Suku Thionghoa Indonesia. JFI, 11(1), 437–445.

Chang, S.A., 2012. Smoking and type 2 diabetic mellitus. Diabetic & Metabolism Journal, 36(6), 399–403.

Chenoweth, M.J., O’Loughlin, J., Sylvestre, M.-P., Tyndale, R.F., 2013. CYP2A6 slow nicotine metabolism is associated with increased quitting by adolescent smokers. Pharmacogenetics and genomics, 23(4), 232–5.

Cho, N.H., Chan, J.C.N., Jang, H.C., Lim, S., Kim, H.L., Choi, S.H., 2009. Cigarette Smoking is An Independent Risk Factor for Type 2 Diabetic : a Four-Year Community-Based Prospective Study. J. Clin. Endocrinol., 71, 679–685.

Devaranavadgi, B.B., Aski, B.S., Kashinath, R.T. and Huntekari, I.A., 2012. Effect of Cigarette Smoking on Blood Lipids – A Study in Belgaum, Northern Karnataka, India. Global Journal of Medical Research, 12(6), 57-61.

Fujieda, M., Yamazaki, H., Saito, T., Kiyotani, K., Gyamfi, M.A., Sakurai, M., Dosaka-Akita, H., Sawamura, Y., Yokota, J., Kunitoh, H., Kamataki, T., 2004. Evaluation of CYP2A6 genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers. Carcinogenesis, 25(12), 2451–2458.

Gudbjornsdottir, Sattar, N., Rawshani, A., Franzén, S., Rawshani, A., Svensson, A. M., Rosengren, A., McGuire, D. K., and Eliasson, B., 2019. Age at Diagnosis of Type 2 Diabetic Mellitus and Associations with Cardiovascular and Mortality Risk. Circulation, 139(19), 2228–2237.

Hong, J.W., Ku, C.R., Noh, J.H., Ko, K.S., Rhee, B.D., Kim, D.J., 2018. Association between Self-Reported Smoking and Hemoglobin A1c in a Korean Population without Diabetic : The 2011 – 2012 Korean National Health and Nutrition Examination Survey. PLoS ONE, 10(5), 1–8.

Houston, T.K., Person, S.D., Pletcher, M.J., Liu, K., Iribarren, C., Kiefe, C.I., 2006. Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study. BMJ, 332(7549), 1064–1069.

Hu, F.B., 2011. Globalization of Diabetic The role of diet , lifestyle , and genes. Diabetic Care, 34(6), 1249–1257.

Hukkanen, J., Jacob, P., Benowitz, N.L., 2005. Metabolism and disposition kinetics of nicotine. Pharmacological reviews, 57(1), 79–115.

International Diabetic Federation, 2021. IDF Western Pacific members [WWW Document]. www.idf.org,. URL https://idf.org/our-network/regions-members/western-pacific/members/104-indonesia.html (accessed 11.19.21).

Kirkman, M.S; Briscoe, V.J; Clark, N.; Florez, H.; Haas, L.B.; Halter, J.B.; Huang, E.S.; Korytkwoski, M.T., Munshi, M.N.; Odegard, P.S.; Pratley, R.E.; Swift, C.S., 2012. Diabetic in Older Adults. Diabetic Care, 35(10), 2650–2664.

Koda, M., Kitamura, I., Okura, T., Otsuka, R., Ando, F., Shimokata, H., 2016. The associations between smoking habits and serum triglyceride or hemoglobin A1c levels differ according to visceral fat accumulation. Journal of Epidemiology, 26(4), 208–215.

Liu, T., Chen, W.-Q., David, S.P., Tyndale, R.F., Wang, H., Chen, Y.-M., Yu, X.-Q., Chen, W., Zhou, Q., Ling, W.-H., 2011. Interaction between heavy smoking and CYP2A6 genotypes on type 2 diabetic and its possible pathways. European journal of endocrinology / European Federation of Endocrine Societies, 165(6), 961–7.

Liu, Y., Xu, Y., Li, F., Chen, H., Guo, S., 2013. CYP2A6 deletion polymorphism is associated with decreased susceptibility of lung cancer in Asian smokers: a meta-analysis. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine, 34(5), 2651–2657.

Lorenzati, B., Zucco, C., Miglietta, S., Lamberti, F., Bruno, G., 2010. Oral hypoglycemic drugs: Pathophysiological basis of their mechanism of action. Pharmaceuticals, 3(9), 3005–3020.

Maddatu, J., Anderson-baucum, E., Evans-molina, C., Physiology, I., 2017. Smoking and the Risk of Type 2 Diabetic. Transl Res., 184, 101–107.

Minematsu, N., Nakamura, H., Furuuchi, M., Nakajima, T., Takahashi, S., Tateno, H., Ishizaka, A., 2006. Limitation of cigarette consumption by CYP2A6*4, *7 and *9 polymorphisms. The European respiratory journal, 27(2), 289–92.

Morimoto, A., Tatsumi, Y., Deura, K., Mizuno, S., Ohno, Y., Watanabe, S., 2013. Impact of cigarette smoking on impaired insulin secretion and insulin resistance in Japanese men: The Saku Study. Journal of Diabetic Investigation, 4(3), 274–280.

Nair, M., Prabhakaran, D., Narayan, K.M.V., Sinha, R., Lakshmy, R., Devasenapathy, N., Daniel, C.R., Gupta, R., George, P.S., Mathew, A., Tandon, N., Reddy, K.S., 2011. HbA(1c) values for defining diabetic and impaired fasting glucose in Asian Indians. Primary Care Diabetic, 5(2), 95–102.

O’Loughlin, J., 2004. Genetically decreased CYP2A6 and the risk of tobacco dependence: a prospective study of novice smokers. Tobacco Control, 13(4), 422–428.

Padmawati, R.S., Ng, N., Prabandari, Y.S., Nichter, M., 2009. Smoking among diabetic patients in Yogyakarta , Indonesia : cessation efforts are urgently needed. Tropical Medicine and International Health, 14(4), 412–419.

Papathanasiou, G., Mamali, A., Papafloratos, S., Zerva, E., 2014. Effects of smoking on cardiovascular function: The role of nicotine and carbon monoxide. Health Science Journal, 8(2), 272–288.

Patramurti, C.. F., 2019. Genetic Polymorphism of Cytochrome P450 2A6 Allele * 4 and * 9 : Study on Glycohemoglobine Level Among Javanese Indonesian Smokers. PSR, 6(2), 82–88.

Patramurti, C., Fenty, F., 2020. Association of Smoking Behaviour and Glycohemoglobine Levels Among Adults Javanese Indonesian Smokers, Jurnal Farmasi Sains dan Komunitas (Journal of Pharmaceutical Sciences and Community), 17(2), 11–13.

Patramurti, C., Nurrochmad, A., Martono, S., Science, P., Mada, G., Chemistry, P., 2015. Poymorphism of Cytochrome P450 2A6 ( CYP2A6 * 1 AND CYP2A6 * 4 ) among Javaneses Indonesia Smoker and Non Smoker. MFI, 26(1), 11–19.

Prajapati, D.D., Anand, D.V.H., Patel, D.M., 2014. Significance of Glycosylated Haemoglobin (Hb) in Diabetic Patients. The Southeast Asian Journal of Case Report and Review, 3(1), 599–608.

R.I., K.K., 2018. Hasil Utama Riskesdas 2018. Badan Penelitian dan Pengembangan Kesehatan, Jakarta.

Raunio, H., Rahnasto-Rilla, M., 2012. CYP2A6: genetics, structure, regulation, and function. Drug Metabolism and Drug Interactions, 27(2), 73–88.

Sarah, K., Shilliday, B.B., 2006. Smoking and Diabetic : Helping Patients Quit. Clinical Diabetic, 24(3), 133–137.

Sargeant, L.A., Khaw, K.-T., Bingham, S., Day, N.E., Luben, R.N., Oakes, S., Welch, A., Wareham, N.J., 2001. Cigarette smoking and glycaemia: the EPIC-Norfolk Study. International Journal of Epidemiology, 30(3), 547–554.

Saudek, C.D., Derr, R.L., Kalyani, R.R., 2006. Assessing glycemia in diabetic using self-monitoring blood glucose and hemoglobin A1c. JAMA, 295(14), 1688–1697.

Schoedel, K. A, Hoffmann, E.B., Rao, Y., Sellers, E.M., Tyndale, R.F., 2004. Ethnic variation in CYP2A6 and association of genetically slow nicotine metabolism and smoking in adult Caucasians. Pharmacogenetics, 14(9), 615–626.

Singh, D., 2016. Effect of Cigarette Smoking on Serum Lipid Profile in Male Population of Udaipur. Biochemistry & Analytical Biochemistry, 5(3), 3–5.

Soelistijo, S.A., Novida, H., Rudijanto, A.; Soewondo, P., Suastika, K., Manaf, A. et al., 2015. Konsensus Pengendalian dan Pencegahan Diabetic Melitus Tipe 2 di Indonesia, 2015, Perkeni.

Somm, E., Schwitzgebel, V.M., Vauthay, D.M., Camm, E.J., Chen, C.Y., Giacobino, J.P., Sizonenko, S. V., Aubert, M.L., Hüppi, P.S., 2008. Prenatal nicotine exposure alters early pancreatic islet and adipose tissue development with consequences on the control of body weight and glucose metabolism later in life. Endocrinology, 149(12), 6289–6299.

Soulimane, S., Simon, D., Shaw, J., Witte, D., Zimmet, P., Vol, S., Borch-Johnsen, K., Magliano, D., Vistisen, D., & Balkau, B. 2011. HbA1c, Fasting Plasma Glucose and The Prediction of Diabetic: Inter99, AusDiab and D.E.S.I.R. Diabetic research and clinical practice, 96(3), 392–9.

Spijkerman, A. M.W., van der A, D. L., Nilsson, P. M., Ardanaz, E., Gavrila, D., Agudo, A., Arriola, L., Balkau, B., Beulens, J. W., Boeing, H., de Lauzon-Guillain, B., Fagherazzi, G., Feskens, E. J., Franks, P. W., Grioni, S., Huerta, J. M., Kaaks, R., Key, T. J., Overvad, K., … Wareham, N. JLvan der A, D., Nilsson, P.M., Ardanaz, E., Gavrila, D., Agudo, A., 2014. Smoking and Long-Term Risk of Type 2 Diabetic : The EPIC- InterAct Study in European Populations. Diabetic Care, 37(12), 3164–3171.

Stadler, M., Tomann, L., Storka, A., Wolzt, M., Peric, S., Bieglmayer, C., Pacini, G., Dickson, S.L., 2014. Effects of Smoking Cessation on b-cell Function, Insulin Sensitivity, Body Weight, and Appetite. Eur J of Endocrinology, 170(2), 219–227.

Willi, C., Bodenmann, P., Ghali, W.A., Faris, P.D., Cornuz, J., 2007. Active smoking and the risk of type 2 diabetic: a systematic review and meta-analysis. JAMA, 298(22), 2654–2664.

Xie, X., Liu, Q., Wu, J., Wakui, M., 2009. Impact of cigarette smoking in type 2 diabetic development. Acta Pharmacologica Sinica, 30(6), 784–787.

Zhao, Y., Song, C., Ma, Xiaokun, Ma, Xiaojun, Wang, Q., Ji, H., Guo, F., Qin, G., 2017. Synergistic Effect of Family History of Diabetic and Dietary Habits on the Risk of Type 2 Diabetic in Central China 2017.




DOI: https://doi.org/10.24071/jpsc.003902

Refbacks

  • There are currently no refbacks.


Copyright (c) 2022 Jurnal Farmasi Sains dan Komunitas (Journal of Pharmaceutical Sciences and Community)

 

 

 

 

 

 

 

  

Jurnal Farmasi Sains dan Komunitas (Journal of Pharmaceutical Sciences and Community)

Published by Faculty of Pharmacy, Universitas Sanata Dharma Yogyakarta

Creative Commons Licence
This work is licensed under a Creative Commons Attribution 4.0 International License.