Submit Manuscript  

Article Details


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

Author(s):

Imadeldin Elfaki*, Rashid Mir, Faisel M. Abu-Duhier, Chandan K. Jha, Adel I. Al-Alawy, Abdullatif Taha Babakr and Salem Abd El-Hadi Habib   Pages 1 - 12 ( 12 )

Abstract:


Background: Cytochrome P450s (CYPs) are drug-metabolizing enzymes catalyzing the metabolism of about 75% of drug in clinical use. CYP2C9 represent 20% total CYP proteins in liver cells and is crucial members of CYPs superfamily. CYP2C19 metabolizes very important drug 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 Tabuk 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=0.97). The genotypes of rs1057910 were not associated with type 2 diabetes (T2D) (P>0.05). Whereas the genotype distribution of rs4986893 in cases and in controls were significantly different (P= 0.0001). 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 in different populations.

Keywords:

CytochromeP450s, CYP2C9, CYP2C19, Gene polymorphisms, Diabetes mellitus, drug metabolism, single nucleotide polymorphisms (SNPs)

Affiliation:

Department of Biochemistry, Faculty of Science, University of Tabuk,, Prince Fahd Ben Sultan Research Chair, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk,, Prince Fahd Ben Sultan Research Chair, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk,, Department of Human Genetics Punjabi University, Punjab., Department of Biochemistry, Faculty of Science, University of Tabuk,, Department of Medical Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Department of Biochemistry, Faculty of Science, University of Tabuk



Read Full-Text article