Genetic Variants Involved in Metformin Pharmacokinetics in the Chilean Population
Abstract
Objective: To estimate the frequency and potential impact of genetic variants involved in metformin pharmacokinetics, including gastrointestinal absorption, renal elimination, and hepatic transport in the Chilean population.
Subjects and methods: The frequency of metformin-related gene variants was estimated using data from a genome-wide, exome-focused genotyping array in 918 participants of the Chilean Growth and Obesity Cohort Study (GOCS). Allele frequencies in Chileans were compared with those published worldwide, and the degree of Amerindian/European ancestry was assessed. A predictive bioinformatic analysis was performed on relevant genetic variants using PolyPhen-2.
Results and discussion: The genetic polymorphism (p.Leu125Phe; p.L125F; rs77474263; C>T) in the SLC47A1 gene (MATE1 transporter) showed a much higher frequency of the 125Phe (T-allele) in the Chilean population (15.3%) than in non-American populations, being virtually absent in Africa, Europe, or Asia. The 125Phe variant was associated with a higher percentage of Amerindian ancestry in the Chilean population. This result is consistent with a previous report indicating that this variant is enriched in Native American populations, given its high frequency among Mestizo and Indigenous populations in Mexico. The functional variant p.125Phe has been previously suggested to promote plasma metformin accumulation, mitochondrial dysfunction, and increased plasma lactate concentrations by altering renal metformin…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 918 participants or records.
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