Genetic CYP2A6 Polymorphism May Worsen Glycohemoglobin Levels: Study among Javanese Indonesian Smokers
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Submitted
19 July 2023
Published
29 February 2024
Keywords:
-
CYP2A6*4, CYP2A6*7, CYP2A6*9, HbA1c levels
Abstract
We have examined the inactive CYP2A6 alleles gene, including CYP2A6*4, CYP2A6*7, and CYP2A6*9, associated with glycohemoglobin levels among Javanese Indonesian smokers. There are 106 smokers participating in this study. Due to the number of cigarettes smoked per day, there are three groups of smokers: light, intermediate, and heavy smokers, with 98.7% being light and intermediated smokers while the rest are heavy smokers. All participants had smoked for more than 10 years, indicating they had been exposed to nicotine for a long time. Based on their genotype, there were four groups of smokers, including fast, intermediate, slow, and poor metabolizers. Most fast and intermediate metabolizers have HbA1c levels in the normal range (<5.7). On the other hand, most slow metabolizers have Hb1c levels >5.7, and all fast metabolizers have HbA1c levels >5.7, indicating that they the prediabetes and diabetes. The chi-square test showed a relationship between CYP2A6 polymorphism and HbA1c levels among the participants (P-value 0.000 <0.005 and χ2=54.6, df=1). The presence of an inactive allele will worsen the HbA1c levels in smokers.
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References
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3. Prabowo MH, Febrinasari RP, Pamungkasari EP, Mahendradhata Y, Pulkki-Brännström AM, Probandari A. Health-related Quality of Life of Patients with Diabetes Mellitus Measured With the Bahasa Indonesia Version of EQ-5D in Primary Care Settings in Indonesia. J Prev Med Public Health. 2023;56(5):467-74. DOI: 10.3961/jpmph.23.229; PMCID: PMC10579634; PMID: 37828874
4. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. 2020;21(17):6275. DOI: 10.3390/ijms21176275; PMCID: PMC7503727; PMID: 32872570
5. Arifin H, Chou KR, Ibrahim K, Fitri SUR, Pradipta RO, Rias YA, et al. Analysis of Modifiable, Non-Modifiable, and Physiological Risk Factors of Non-Communicable Diseases in Indonesia: Evidence from the 2018 Indonesian Basic Health Research. J Multidiscip Healthc. 2022;15:2203-21. DOI: 10.2147/jmdh.s382191; PMCID: PMC9532265; PMID: 36213176
6. Patramurti C, Virginia DM, Fenty F, Setiawan CH, Julianus J, Hendra P, et al. 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. J Farmasi Sains Komunitas JFSK. 2022;19(2):53-61. DOI: 10.24071/jpsc.003902
7. Liu X, Bragg F, Yang L, Kartsonaki C, Guo Y, Du H, et al. Smoking and smoking cessation in relation to risk of diabetes in Chinese men and women: a 9-year prospective study of 0·5 million people. Lancet Public Health. 2018;3(4):167–76. DOI: 10.1016/s2468-2667(18)30026-4; PMCID: PMC5887081; PMID: 29548855
8. Hong JW, Ku CR, Noh JH, Ko KS, Rhee BD, Kim DJ. Association between self-reported smoking and hemoglobin A1c in a Korean population without diabetes: The 2011-2012 Korean national health and nutrition examination survey. PLoS One. 2015;10(5):e0126746. DOI: 10.1371/journal.pone.0126746; PMCID: PMC4444290; PMID: 26011526
9. Vlassopoulos A, Lean MEJ, Combet E. Influence of Smoking and Diet on Glycated Haemoglobin and 'Pre-Diabetes’ Categorisation: A Cross-Sectional Analysis. BMC Public Health. 2013;13:1013. DOI: 10.1186/1471-2458-13-1013; PMCID: PMC4029457; PMID: 24499114
10. Kaiafa G, Veneti S, Polychronopoulos G, Pilalas D, Daios S, Kanellos I, et al. Is HbA1c an ideal biomarker of well-controlled diabetes? Postgrad Med J. 2021;97(1148):380-3. DOI: 10.1136/postgradmedj-2020-138756; PMCID: PMC10016911; PMID: 32913038
11. Kaplan AK, Sezgin Y. Evaluation of the Relationship Between Smoking and Insulin Resistance: A Case-Control Study. Cureus. 2023;15(3):e36684. DOI: 10.7759/cureus.36684; PMCID: PMC10039987; PMID: 36987444
12. Benowitz NL, St Helen G, Dempsey DA, Jacob 3rd P, Tyndale RF. Disposition kinetics and metabolism of nicotine and cotinine in African American smokers: impact of CYP2A6 genetic variation and enzymatic activity. Pharmacogenet Genomics. 2016;26(7):340-50. DOI: 10.1097/fpc.0000000000000222; PMCID: PMC4892970; PMID: 27035242
13. Patramurti C, Fenty F. Genetic Polymorphism Cytochrome P4502a6 Allel *4 And *9: Studi On Glycohemoglobine Level Among Javanese Indonesian Smokers. Pharm Sci Res. 2019;6(2):82-8. DOI: 10.7454/psr.v6i2.4488
14. Liu T, Xie C-B, Ma W-J, Chen W-Q. Association between CYP2A6 genetic polymorphisms and lung cancer: a meta-analysis of case-control studies. Environ Mol Mutagen. 2013;54(2):133–40. DOI: 10.1002/em.21751; PMID: 23203414
15. Patramurti C, Nurrochmad A, Martono S, Science P, Mada G, Chemistry P. Polymorphism of Cytochrome P450 2A6 (CYP2A6*1 and CYP2A6*4) among Javanese Indonesian Smoker and Non Smoker. Indones J Pharm. 2015;26(1):11–9. DOI: 10.14499/indonesianjpharm26iss1pp11
16. Patramurti C, Fenty F. Association of Smoking Behaviour and Glycohemoglobine Levels Among Adults Javanese Indonesian Smokers. J Farmasi Sains Komunitas JFSK. 2020;17(2):76–85. DOI: 10.24071/jpsc.002408
17. Patramurti C, Virginia DM. Distribution of cytochrome P450*4 (CYP2A6*4) allele gene among Javanese Indonesian T2DM patients. Pharmaciana. 2021;11(1):25–38. DOI: 10.12928/pharmaciana.v11i1.18468
18. Aryanti GAKW, Priastana IKA. Modified Fagerstrom Tolerance Questionnaire (Adolescents) Indonesian Version: Validity and Reliability Study. Indones J Health Res. 2019;2(1):16-22. DOI: 10.32805/ijhr.2019.2.1.28
19. Feng X, Qian Z, Zhang B, Guo E, Wang L, Liu P, et al. Number of Cigarettes Smoked Per Day, Smoking Index, and Intracranial Aneurysm Rupture: A Case-Control Study. Front Neurol. 2018;9:380. DOI: 10.3389/fneur.2018.00380; PMCID: PMC5990590; PMID: 29904368
20. Lin M, Chu M, Li X, Ma H, Fang Z, Mao L, et al. Factors influencing adolescent experimental and current smoking behaviors based on social cognitive theory: A cross-sectional study in Xiamen. Front Public Health. 2023;11:1093264. DOI: 10.3389/fpubh.2023.1093264; PMCID: PMC10073720; PMID: 37033036
21. Noubiap JJ, Nansseu JR, Endomba FT, Ngouo A, Nkeck JR, Nyaga UF, et al. Active smoking among people with diabetes mellitus or hypertension in Africa: a systematic review and meta-analysis. Sci Rep. 2019;9(1):588. DOI: 10.1038/s41598-018-37858-z; PMCID: PMC6345945; PMID: 30679752
22. Akter S, Goto A, Mizoue T. Smoking and the risk of type 2 diabetes in Japan: A systematic review and meta-analysis. J Epidemiol. 2017;27(12):553–61. DOI: 10.1016/j.je.2016.12.017; PMCID: PMC5623034; PMID: 28716381
23. Akkuzulu H, Aypak C, Özdemir A, Görpelioǧlu S. Impact of smoking and nicotine addiction on HbA1clevels and diabetic microvascular complications. Clin Diabetol. 2020;9(2):112–7. DOI: 10.5603/DK.2020.0004
24. Maddatu J, Anderson-baucum E, Evans-molina C, Physiology I. Smoking and the Risk of Type 2 Diabetes. Transl Res. 2017;184:101–7. DOI: 10.1016/j.trsl.2017.02.004; PMCID: PMC5429867; PMID: 28336465
25. Campagna D, Alamo A, Pino A Di, Russo C, Calogero AE, Purrello F, et al. Smoking and diabetes: dangerous liaisons and confusing relationships. Diabetol Metab Syndr. 2019;11:85. DOI: 10.1186/s13098-019-0482-2; PMCID: PMC6813988; PMID: 31666811
26. Yuan S, Larsson SC. A causal relationship between cigarette smoking and type 2 diabetes mellitus: A Mendelian randomization study. Sci Rep. 2019;9(1):19342. DOI: 10.1038/s41598-019-56014-9; PMCID: PMC6920406; PMID: 31852999
27. Sliwińska-Mossoń M, Milnerowicz H. Influence of tobacco smoking on lipase activity in patients with pancreatitis. Przegla̧d Lek. 2005;62(10):1058–61. PMID: 16521953
28. Bajaj M. Nicotine and Insulin Resistance: When the Smoke Clears. Diabetes. 2012;61(12):3078–80. DOI: 10.2337/db12-1100; PMCID: PMC3501863; PMID: 23172960
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Authors
1.
Patramurti C, Virginia DM. Genetic CYP2A6 Polymorphism May Worsen Glycohemoglobin Levels: Study among Javanese Indonesian Smokers. Borneo J Pharm [Internet]. 2024Feb.29 [cited 2024Nov.8];7(1):29-3. Available from: https://journal.umpr.ac.id/index.php/bjop/article/view/5467
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