Background: A promoter variable number tandem repeat polymorphism (pVNTR) of CYP2C9 is described with three types of fragments: short (pVNTR-S), medium (pVNTR-M) and long (pVNTR-L). The pVNTR-S allele reduces the CYP2C9 mRNA level in the human liver, and it was found to be in high linkage disequilibrium (LD) with the CYP2C9*3 allele in a White American population. The aim of the present study is to determine the presence and frequency of CYP2C9pVNTR in a Spanish population, as well as analyzing whether the pVNTR-S allele is in LD with the CYP2C9*3 allele in this population.
Subjects and methods: A total of 209 subjects from Spain participated in the study. The CYP2C9 promoter region was amplified and analyzed using capillary electrophoresis. Genotyping for CYP2C9*2 and *3 variants was performed using a fluorescence-based allele-specific TaqMan allelic discrimination assay.
Results: The frequencies of CYP2C9pVNTR-L, M and S variant alleles are 0.10, 0.82 and 0.08, respectively. A high LD between CYP2C9pVNTR-S and CYP2C9*3 variant alleles is observed (D' = 0.929, r2 = 0.884).
Conclusion: The results from the present study show that both CYP2C9pVNTR and CYP2C9*3 are in a high LD, which could help to better understand the lower metabolic activity exhibited by CYP2C9*3 allele carriers. These data might be relevant for implementation in the diverse clinical guidelines for the pharmacogenetic analysis of the CYP2C9 gene before treatment with different drugs, such as non-steroidal anti-inflammatory drugs, warfarin, phenytoin and statins.
Keywords: CYP2C9; linkage disequilibrium; pVNTR; promoter variable tandem repeat polymorphism.