Analysis of the Potential Association of Drug-Metabolizing Enzymes CYP2C9*3 and CYP2C19*3 Gene Variations With Type 2 Diabetes: A Case-Control Study

Title:Analysis of the Potential Association of Drug-Metabolizing Enzymes CYP2C9*3 and CYP2C19*3 Gene Variations With Type 2 Diabetes: A Case-Control Study

Volume: 21 Issue: 14

Author(s): Imadeldin Elfaki*, Rashid Mir, Faisel Mohammed Abu-Duhier, Chandan Kumar Jha, Adel Ibrahim Ahmad Al-Alawy, Abdullatif Taha Babakr and Salem Abd El-Hadi Habib

Affiliation:

• Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk,Saudi Arabia

Keywords: CytochromeP450s, CYP2C9 , CYP2C19 , gene polymorphisms, diabetes mellitus, drug metabolism, single nucleotide polymorphisms (SNPs).

Abstract: Background: Cytochrome P450s (CYPs) are drug-metabolizing enzymes catalyzing the metabolism of about 75% of drug in clinical use. CYP2C9 represents 20% CYP proteins in liver cells and is a crucial member of CYPs superfamily. CYP2C19 metabolizes very important drugs such as antiulcer drug omeprazole, the antiplatelet drug clopidogrel and anticonvulsant mephenytoin. Single nucleotide polymorphisms (SNPs) of CYP genes have been associated with unexpected drug reactions and diseases in different populations.

Objective: We examined the associations of CYP2C9*3 (rs1057910) and CYP2C19*3 (rs4986893) with T2D in Saudi population.

Methods: We used the allele-specific PCR (AS-PCR) and DNA sequencing in 111 cases and 104 controls for rs1057910, and in 119 cases and 110 controls for rs4986893.

Results: It is indicated that the genotype distribution of rs1057910 in cases and controls were not significantly different (P=0.0001). The genotypes of rs1057910 were not associated with type 2 diabetes (T2D) (P>0.05). Whereas the genotype distribution of rs4986893 in cases and controls was significantly different (P=0.049). The AA genotype of rs4986893 may be associated in increased risk to T2D with OR=17.25 (2.06-143.8), RR=6.14(0.96-39.20), P=0.008.

Conclusion: The CYP2C9*3 (rs1057910) may not be associated with T2D, while CYP2C19*3 (rs4986893) is probably associated with T2D. These findings need to be validated in follow-up studies with larger sample sizes and different populations.

Cite this article as:

Elfaki Imadeldin *, Mir Rashid , Abu-Duhier Mohammed Faisel , Jha Kumar Chandan , Ahmad Al-Alawy Ibrahim Adel , Babakr Taha Abdullatif and Habib Abd El-Hadi Salem , Analysis of the Potential Association of Drug-Metabolizing Enzymes CYP2C9*3 and CYP2C19*3 Gene Variations With Type 2 Diabetes: A Case-Control Study, Current Drug Metabolism 2020; 21 (14) . https://dx.doi.org/10.2174/1389200221999201027200931

DOI https://dx.doi.org/10.2174/1389200221999201027200931	Print ISSN 1389-2002
Publisher Name Bentham Science Publisher	Online ISSN 1875-5453