RESUMEN
Introduction: Pharmacogenetic markers, such as the ATP Binding Cassette (ABCB1) and cytochrome P450 (CYP) 3A5 enzymes, play a crucial role in personalized medicine by influencing drug efficacy and toxicity based on individuals' or populations' genetic variations.This study aims to investigate the genetic polymorphisms of CYP3A5 (rs776746) and ABCB1 (rs1045642) in the West Algerian population and compare the genotypes and allelic distributions with those of various ethnic groups. Methods: The study involved 472 unrelated healthy subjects from the Western Algerian population. DNA genotyping was performed using TaqMan allelic discrimination assay. The variants in our population were compared to those in other ethnic groups available in the 1000 Genomes Project. Genotype and allele frequencies were calculated using the chi-square test and the Hardy-Weinberg equilibrium (HWE). Results: The minor allele frequencies were found to be 0.21 for CYP3A5 6986A and 0.34 for ABCB1 3435T. These frequencies were similar to those observed in North African populations, while notable differences were observed in comparison to certain Caucasian and African populations. Conclusion: The difference in the allelic and genotypic distribution of these polymorphisms emphasize the need for dose adjustments in drugs metabolized by CYP3A5 and transported by ABCB1 to optimize treatments outcomes.
Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP , Citocromo P-450 CYP3A , Frecuencia de los Genes , Genotipo , Polimorfismo de Nucleótido Simple , Humanos , Citocromo P-450 CYP3A/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Argelia , Masculino , Femenino , Adulto , Farmacogenética , Persona de Mediana Edad , Población Negra/genética , Alelos , Adulto JovenRESUMEN
BACKGROUND: Coronary Heart Disease (CHD) is a major cause of morbidity and mortality over the world; intermediate traits associated with CHD commonly studied can be influenced by a combination of genetic and environmental factors. OBJECTIVE: We found previously significant association between three genetic polymorphisms, and the lipid profile variations in the Algerian population. Considering these findings, we therefore decided to assess the relationships between these polymorphisms and CHD risk. METHODS: We performed a population-based, cross-sectional study, of 787 individuals recruited in the city of Oran, in which, a nested case-control study for MetS, T2D, HBP, obesity and CHD were performed. Subjects were genotyped for four SNP rs7412, rs429358 rs4420638 and rs439401 located in the 19q13.32 region. RESULTS: The T allele of rs439401 confers a high risk of hypertension with an odds ratio (OR) of 1.46 (95% CI [1.12-1.9], p = 0.006) and the G allele of rs4420638 was significantly associated with a decreased risk of obesity, OR 0.48 (95% CI [0.29-0.81], p = 0.004). No associations were found for MetS, T2D and CHD. CONCLUSION: Although the studied genetic variants were not associated with the risk of CHD, the 19q13.32 locus was associated with some of the cardiometabolic disorders in Algerian subjects.