Investigating C23237T Polymorphism of Cyp3a4 Gene in Healthy People of West Mazandaran in Terms of Age and Gender
Subject Areas :
Journal of Animal Biology
Fatemeh Heidarian
1
,
Vida Hojati
2
,
Reza Golijani Moghadam
3
1 - Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
2 - Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
3 - Department of Biology, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
Received: 2022-09-14
Accepted : 2023-01-08
Published : 2023-08-23
Keywords:
gender,
polymorphism,
genotype,
Cyp3a4,
ARMS-PCR,
Abstract :
CYP3A4 gene is located on chromosome 7 and the largest number of substrates among cytochrome p450 enzymes belongs to it. The CYP3A4 gene is present in the endoplasmic reticulum of all tissues except the brain, although the main place of accumulation of its protein is in the liver and prostate. Because there have not been many studies on the polymorphisms of this gene, especially in Iran, this study was conducted in order to investigate the C23237T polymorphism of Cyp3a4 gene in 103 healthy male and female subjects aged 7 months to 79 years-old in the west of Mazandaran. In this research, whole blood was collected from healthy male and female individuals in the western cities of Mazandaran province. For each person, information related to age, sex, family history, alcohol and tobacco consumption, and the patient's medication were recorded. ARMS-PCR technique was used in this study. Data analysis was done using SPSS 2016 software and chi square test. The significant level of polymorphism relationship with gender and age of people was considered as p < 0.05. The results of the research showed that 70 people had the heterozygous status of the mutated AG genotype, the frequency of which was 67.96%. There was no significant relationship between genotype frequency and patients' age. Also, there is no significant relationship between C23237T polymorphism of Cype3a4 gene with age (p = 0.81) and gender (p = 0.845). According to the results of this research, it can be considered that people in any age group and with any gender have the same probability of contracting the disease.
References:
Assis J, Pereira D., Gomes M., Marques D., Marques I., Nogueira A., Catarino R., Medeiros R. 2013. Influence of CYP3A4 genotypes in the outcome of serous ovarian cancer patients treated with first-line chemotherapy: implication of a CYP3A4 activity profile. International Journal of Clinical and Experimental Medicine, 6(7):552-561.
Barnes H.J., Jenkins C.M., Waterman M.R. 1994. Baculovirus expression of bovine cytochrome P450c17 in Sf9 cells and comparison with expression in yeast, mammalian cells, and coli. Archives of Biochemistry and Biophysics, 315:489-494.
Bozina N., Granić P., Lalić Z., Tramisak I., Lovrić M., Stavljenić-Rukavina A. 2003. Genetic polymorphisms of cytochromes P450: CYP2C9, CYP2C19, and CYP2D6 in Croatian population. Croatian Medical Journal, 44(4):425-428.
Bull L. 2013. Genetics, Mutations, and Polymorphisms. Landes Bioscience. Bookshelf ID: NBK6475.
Cavaco I., Piedade R., Gil P. 2006. Cyp2c8 polymorphism among the Portuguese. Clinical Chemistry and Laboratory Medicine, 44(2):168-170.
Dai D., Darryl C., Joyce A., Sherry J. 2001. Polymorphisms in human cyp2c8 decrease metabolisms of the anticancer drug pactitaxel and arachidonic acid. Pharmacogenetics, 11:597-607.
Dally H., Edler L., Jäger B., Schmezer P., Spiegelhalder B., Dienemann H., Drings P., Schulz V., Kayser K., Bartsch H., Risch A. 2003. The CYP3A4*1B allele increases risk for small cell lung cancer: effect of gender and smoking dose. Pharmacogenetics, 13(10):607-18.
Danielson PB .2002. The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans. Current Drug Metabolism, 3:561-597.
Evans W.E., Relling M.V. 2004. Moving towards individualized medicine with pharmacogenomics. Nature, 429: 464- 468.
Fintan R. 2009. personalized medicine: something old, something new. Personalized Medicine, 6:1-5.
Floriano-Sanchez E, Rodriguez NC, Bandala C, Coballase-Urrutia E, Lopez-Cruz J. 2014. CYP3A4 expression in breast cancer and its association with risk factors in Mexican women. Asian Pacific Journal of Cancer Prevention, 15(8):3805-3809.
Ghias-Tabari R. 2012. Investigation of genetic polymorphisms of cytochrome P450 enzyme (2C19) in Turkmen and Fars people. Master's Thesis in Clinical Biochemistry, Golestan University of Medical Sciences, 83 p.
Goldstein J.A. 2001. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. British Journal of Clinical Pharmacology, 52: 349-355.
Golestanian R., Barzegar A., Rahimi Q., Ebrahimzadeh M.A. The relationship between methylation of the promoter region of the cyp3a4 gene and the occurrence of gastric cancer in Mazandaran province.International Conference on Agricultural Sciences, Medicinal Plants and Traditional Medicine.
Gréen H., Söderkvist P., Rosenberg P., Mirghani R.A. .2009. Pharmacogenetic studies of Paclitaxel in the treatment of ovarian cancer. Basic Clinical Pharmacology and Toxicology, 104:130-137.
Hamzei H., Dastmalchi S. Analysis of the arrangement of three heterozygous mutations in human cpy3a4 female with long distances from each other.Journal of Pharmaceutical Sciences, 11(4):63-69.
Hashimoto H., Toide K., Kitamura R., Fujita M., Tagawa S., Itoh S., Kamataki T. 1993. Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control. European Journal of Biochemistry, 218(2): 585-595.
Heydari Qaraei H., Rashki A., Bahari A., Rashki Ghaleno Z. Investigation of genetic variation in CYP3A4 gene and its relationship with type 2 diabetes in Sistan and Baluchistan province.Diabetes Nursing, 6(3):538-538.
Hojgard L., Zic Fuchs M., Gyllenberg M. 2012. Personalised Medicine for the European Citizen.European Science Foundation. esf.org.
Hosani J., Nasiri M. Homology and functional region prediction in CYP3A4 and CYP2D6 genes and their comparison in human, cow and chicken.International Conference on Research in Engineering, Science and Technology, https://civilica. com/ doc/398475.
Hosseini S.S., Keyhanian S., Vosoughi E., Ahangar N. 2018. Polymorphisms of CYP1A1 Gene Variants m1 and m2 and Their Association with the Incidence of Cancer in West of Mazandaran Province, Iran. Journal of Mazandaran University of Medical Science, 28(165):57-68.
Keshava C., McCanlies E.C., Weston A. 2004. CYP3A4 polymorphisms--potential risk factors for breast and prostate cancer: a HuGE review. American Journal of Epidemiology, 160(9):825-41.
Lee S.J., Goldstein JA. 2005. Functionally defective or altered CYP3A4 and CYP3A5 single nucleotide polymorphisms and their detection with genotyping tests. Pharmacogenomics, 6(4):357–71.
Luo G., Cunningham M., Kim S., Burn T, Lin J., Sinz M., Hamilton G., Rizzo C., Jolley S., Gilbert D., Downey A., Mudra D., Graham R., Carroll K., Xie J., Madan A., Parkinson A., Christ D., Selling B., LeCluyse E., Gan L.S. 2002. CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metabolism and Disposition, 30(7):795-804.
Onsori K., Bakhtiari Tajar M., Haji Z., Nouri M.Investigation of genetic polymorphism of CYP3A4 gene in patients with bladder cancer.Genetics in the Third Millennium, 12(3): 3612-3621.
Paul R. 2015. Orttize Montellano Editor Cyto chrome P450. 4th edition. New York. Springer Cham Heidelberg Dordrecht London. 912 p.
Schork N.J., Fallin D., Lanchbury S. 2000. Single nucleotide polymorphisms and the future of genetic epidemiology. Clinical Genetics, 58:250-264.
Spurdle A.B., Goodwin B., Hodgson E., Hopper J.L., Chen X., Purdie D.M., McCredie M.R., Giles G.G., Chenevix-Trench G., Liddle C. 2002. The CYP3A4*1B polymorphism has no functional significance and is not associated with risk of breast or ovarian cancer. Pharmacogenetics, 12(5):355-66.
Such E., Cervera J., Terpos E. 2011. Cyp2c8 gene polymorphism and biosphonate related osteonecrosis of jaw in patients with multiple myeloma. Haematologica, 96(10):1557-9.
Takeshita A., Igarashi-Migitaka , Koibuchi N., Takeuchi Y. 2013. Mitotane induces CYP3A4 expression via activation of the steroid and xenobiotic receptor. Jornal of Endocrinlogy, 216:297-305.
Totah R.A., Rettie A.E. 2005. Cytochrome P450 2C8: substrates, inhibitors, pharmacogenetics, and clinical relevance. Clinical Pharmacology and Therapeutics, 77: 341-352.
Watkins P.B. 1994. Noninvasive tests of CYP3A enzymes. Pharmacogenetics, 4(4):171-184.
_||_