Polymorphic analysis of CYP2C9 gene in Vietnamese population

Area of Science:

• Pharmacogenomics
• Human Genetics
• Drug Metabolism

Background:

• Cytochrome P450 family 2 subfamily C member 9 (CYP2C9) genetic variations significantly influence drug metabolism and patient response.
• Previous research on CYP2C9 polymorphisms in Vietnam primarily focused on common alleles in the Kinh population, leaving a gap in understanding ethnic group diversity.
• Comprehensive data on the complete spectrum of CYP2C9 gene polymorphism across various Vietnamese ethnic groups is lacking.

Purpose of the Study:

• To investigate the genetic distribution and spectrum of CYP2C9 polymorphisms in different ethnic groups within Vietnam.
• To identify novel CYP2C9 variants and characterize their potential functional impact.
• To compare the prevalence of common CYP2C9 variants in Vietnam with global populations for optimized drug therapy.

Main Methods:

• Sequencing of the promoter region and all exons of the CYP2C9 gene in 100 Kinh subjects.
• Analysis of common CYP2C9 variants (*2 and *3) using RFLP-PCR in 194 Kinh and 279 individuals from four other ethnic groups.
• In silico functional analysis (SIFT, Polyphen-2) of identified novel variants.

Main Results:

• Seven previously reported CYP2C9 alleles and two genotypes were identified in Kinh subjects, with CYP2C9*1 at 96.5% and CYP2C9*3 at 3.5%.
• A novel non-synonymous variant (Pro363His) in exon 7 was discovered, predicted to be intolerant and potentially damaging.
• The prevalence of CYP2C9*2 in the Vietnamese population was found to be significantly lower than in South/West Asian and European populations.

Conclusions:

• This study provides a comprehensive overview of CYP2C9 genetic polymorphism distribution across diverse Vietnamese ethnic groups.
• The identification of a novel, potentially damaging CYP2C9 variant highlights the need for further investigation into its clinical implications.
• The findings offer valuable genetic information crucial for tailoring drug therapies and improving patient outcomes in Vietnam.