Pharmacogenetics of CYP2C19*17: Functional and Clinical Implications of CYP2C19*17 - rs12248560 (c.-806C>T) in the Development of Type 2 Diabetes

The prevalence of diabetes mellitus (DM) is increasing worldwide including Saudi Arabia. DM increases mortality rate, morbidity and vascular complications, accompanied by poor general health status and low quality of life. CYP2C19*17 polymorphism in CYP2C19 gene is associated with the clinical outcome of drugs that are substrates of CYP2C19. CYP2C19*17 confers reduced susceptibility to certain illnesses. This research was conducted to develop a robust method to genotype the rs12248560 single nucleotide variation (SNV). We enrolled 206 subjects: 100 subjects were clinically confirmed cases of type 2 diabetes (T2D), and 106 subjects were healthy controls in this study. Samples from all subjects were screened for the CYP2C19 rs12248560 (c.-806C>T) by the amplification-refractory mutation system PCR (ARMS-PCR). The frequencies of CYP2C19*17 TT, CT, CC genotypes in T2D cases were 12%, 21%, and 67%, respectively whereas those in healthy controls were 70.75%, 26.41%, and 2.83%, respectively. The difference was significant (p < 0.035). T allele (fT) prevalence was found to be substantially greater in T2D cases compared to healthy controls (0.22 vs. 0.16). Results indicated that the CYP2C19*17 - TT genotype is associated with increased susceptibility to T2D with OR = 4.47, RR = 2.64, (p < 0.024). Moreover, the ARMS-based assay proved to be an easy method for the determination of CYP2C19*17 genotypes with reduced cost and good accuracy. In addition, this result helps in the detection and stratification of the individuals who are at risk for the development of T2D. Nevertheless, this finding needs to be validated in molecular genetic studies with increased specimen size and in different ethnicities.