Association of CYP2C19 genotype with type 2 diabetes

Abstract

Background: CYP2C19 is a major isoform of cytochrome P450 that metabolizes a number of commonly prescribed drugs such as omeprazole, diazepam, tolbutamide and propranolol. Its expression is regulated by the constitutive androstane receptor (CAR), involved in glucocorticoids synthesis. Since a number of crossliniks have been described for CYPs and some hormones, an association of CYP2C19 with type 2 diabetes is likely. Methods: Two groups were studied, 352 diagnosed with type 2 diabetes patients and 342 healthy volunteers form Mexico City. Both groups were tested for CYP2C19*2 and *3 alleles. We carried out an allelic discrimination using TaqMan assay for *2, and used FRET sensor and anchor probes for *3. Results: Ninety one percent of the subjects had the wild type allele, 9% have the *2 allele; no subject presented the *3 allele. The CYP2C19*2 allele is associated with type 2 diabetes (p = 0.012). Admixmap program was used to correct the admixture of this population and get the correlation. This was further confirmed in a linear model with a 67% power and by the method of Strom and Wienker for association on subjects within the mean range of Amerindian ancestry only (60%). Conclusion: Type 2 diabetes patients have significatly more *2 allele than healthy volunteers, more evident for the patients with the homocygous genotype.