Pharmacogenetics and Molecular Ancestry of SLC22A1, SLC22A2, SLC22A3, ABCB1, CYP2C8, CYP2C9, and CYP2C19 in Ecuadorian Subjects with Type 2 Diabetes Mellitus.

Abstract

Background/Objectives: In Ecuador, the prevalence of type 2 diabetes mellitus (T2DM) is the second leading cause of death after ischemic heart disease. Genetic variability in protein-coding genes, single nucleotide variants (SNVs), influences the response to antidiabetic drugs. The frequency of SNVs varies among different populations, so studying the ancestral proportions among SNVs is important for personalized medicine in the treatment of T2DM. This study aimed to evaluate the distribution of Native American, European, and African (NATAM, EUR, and AFR) ancestry in 23 allelic variants of the seven genes that encode the relevant enzymes that metabolize antidiabetic drugs in an Ecuadorian population. Methods: Twenty-three allelic variants of seven genes were analyzed in 297 patients with T2DM from Ecuador, and the molecular ancestry of the samples was analyzed considering three ancestral groups, NATAM, EUR, and AFR using 90 ancestry informative markers (AIMs). Allele and ancestry distributions were analyzed using Spearman's correlation. Results: The Ecuadorian population presents NATAM (61.33%), EUR (34.48%), and AFR (2.60%) ancestry components. CYP2C8*1 and CYP2C9*1 were positively related to NATAM ancestry, while CYP2C8*4 and CYP2C9*2 were positively related to EUR ancestry. CYP2C19*17 was positively correlated to AFR ancestry. The correlation of SLC22A1 variants such as A in rs594709 was positively correlated with NATAM, while GAT in rs72552763 was positive for EUR. The G variant of rs628031 of the SLC22A1 gene was positively correlated with NATAM and negatively correlated with EUR. The C variant of rs2076828 of the SLC22A3 gene was positively correlated with NATAM ancestry. Conclusions: In the Ecuadorian population, a predominance of Native American ancestry has been observed. Among the allelic variants related to enzymes that metabolize antidiabetic drugs, a relationship has been observed between this ancestral component and variants of the CYP2C8*1, CYP2C9*1, SLC22A1 (rs594709 and rs628031), and SLC22A3 (rs2076828) genes. This information is fundamental for the development of strategies for the implementation of personalized medicine programs for Latin American patients.