Genetic polymorphisms and haplotypes of the organic cation transporter 1 gene (SLC22A1) in the Xhosa population of South Africa

Abstract

Human organic cation transporter 1 is primarily expressed in hepatocytes and mediates the electrogenic transport of various endogenous and exogenous compounds, including clinically important drugs. Genetic polymorphisms in the gene coding for human organic cation transporter 1, SLC22A1, are increasingly being recognized as a possible mechanism explaining the variable response to clinical drugs, which are substrates for this transporter. The genotypic and allelic distributions of 19 nonsynonymous and one intronic SLC22A1 single nucleotide polymorphisms were determined in 148 healthy Xhosa participants from South Africa, using a SNAPshot® multiplex assay. In addition, haplotype structure for SLC22A1 was inferred from the genotypic data. The minor allele frequencies for S14F (rs34447885), P341L (rs2282143), V519F (rs78899680), and the intronic variant rs622342 were 1.7%, 8.4%, 3.0%, and 21.6%, respectively. None of the participants carried the variant allele for R61C (rs12208357), C88R (rs55918055), S189L (rs34104736), G220V (rs36103319), P283L (rs4646277), R287G (rs4646278), G401S (rs34130495), M440I (rs35956182), or G465R (rs34059508). In addition, no variant alleles were observed for A306T (COSM164365), A413V (rs144322387), M420V (rs142448543), I421F (rs139512541), C436F (rs139512541), V501E (rs143175763), or I542V (rs137928512) in the population. Eight haplotypes were inferred from the genotypic data. This study reports important genetic data that could be useful for future pharmacogenetic studies of drug transporters in the indigenous Sub-Saharan African populations.

Association of the Reduced Function Met420del Polymorphism of SLC22A1 with Metformin-Induced Gastrointestinal Intolerance in Ethiopian Patients with Type 2 Diabetes Mellitus

“…14 To address this issue, the reduced function methionine deletion at codon 420 (Met420del) variant of SLC22A1 (rs72552763) was selected for this study since its allele frequency is higher in Ethiopian population as compared to other African population. [23][24][25] Furthermore, Met420del is the most studied functional variant of SLC22A1 gene for its influence on metformin pharmacokinetics though there were inconsistent reports based an extensive survey of recent literature. In addition, this variant is generally observed in combination with a rare loss of function polymorphism, Cys88Arg (rs55918055), that causes improper membrane localization of OCT1, resulting in metformin gastrointestinal intolerance.…”

Pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) in newly diagnosed Indian type 2 diabetes patients undergoing metformin monotherapy

“…Solute carrier family 22 member 1 ( SLC22A1 ) gene encodes the organic cation transporter 1 (OCT1), which is expressed on the sinusoidal membrane of hepatocytes. OCT1 mediates the electrogenic transport of drugs [5].…”

<p><em>SLC22A1</em> And<em> ATM</em> Genes Polymorphisms Are Associated With The Risk Of Type 2 Diabetes Mellitus In Western Saudi Arabia: A Case-Control Study</p>

“…The human SLC22A1 gene is located on chromosome 6q25.3 and encodes for organic cation transporter 1 (OCT1); it consists of 11 exons spanning 37 kb and has been shown to play an important role in the control of the glycemic response of T2DM 9. Population studies have shown a high level of polymorphisms for SLC22A1 in different ethnicities 10,11…”