Molecular Ancestry Across Allelic Variants of SLC22A1, SLC22A2, SLC22A3, ABCB1, CYP2C8, CYP2C9, and CYP2C19 in Mexican-Mestizo DMT2 Patients

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Background/Aims: across protein-coding genes, single nucleotide allelic variants (SNVs) affect antidiabetic drug pharmacokinetics, thus contributing to interindividual variability in drug response. SNV frequencies vary across different populations. Studying ancestry proportions among SNV genotypes is particularly important for personalising diabetes mellitus type 2 (DMT2) treatment. Methods: a sample of 249 Mexican DMT2 patients was gathered. SNVs were determined through real-time PCR (RT-PCR). Molecular ancestries were determined as 3 clusters (Native-American, European, and African) based upon 90 ancestry markers (AIMS). Statistical inference tests were performed to analyse ancestry across 23 SNV genotypes. Allele and ancestry distributions were analysed through Spearman’s correlation. Results: ancestry medians were 65.48% Native-American (NATAM), 28.34% European (EUR), and 4.8% African (AFR). CYP2C8*3 and CYP2C8*4 were negatively correlated to NATAM, whereas positively to EUR. The activity score of CYP2C9 was correlated to NATAM (Rho = 0.131, p = 0.042). CYP2C19*17 and the activity score of CYP2C19 were negatively correlated to NATAM. The correlation throughout SLC22A1 variants, such as GAT in rs72552763, was positive by EUR, while A in rs594709 was negative thereby and positive by NATAM. SLC22A3 variant C in rs2076828 was positively correlated to NATAM. NATAM patients present higher HbA1c levels with respect to Mestizo patients (p = 0.037). Uncontrolled patients (HbA1c ≥ 7%) have a larger NATAM ancestry (p = 0.018) and lower EUR (p = 0.022) as compared to controlled patients (HbA1c < 7%). Conclusions: there is a correlation between ancestry and some pharmacokinetically relevant alleles among Mexican DMT2 patients. Ethnicity is relevant for personalised medicine across different populations.