Comment on Dawed et al. Genome-Wide Meta-Analysis Identifies Genetic Variants Associated With Glycemic Response to Sulfonylureas. Diabetes Care 2021;44:2673–2682
Year: 2022
Type: letter
Abstract: We read with interest the article by Dawed et al. ( 1) reporting genetic variants associated with sulfonylurea response in a genome-wide meta-analysis of White Europeans.The C allele of rs10770791 in the intronic region of solute carrier organic anion transporter family member 1B1 (SLCO1B1) was identified as one of two loci associated with improved HbA 1c response.Interestingly, two wellestablished nonsynonymous variants of SLCO1B1, rs4149056 (*5, c.521T>C, p.V174A) and rs2306283 (*37; c.388A>G, p.N130D), in partial link disequilibrium with rs10770791, were not significantly associated with sulfonylurea response based on individual-level data (n 5 3,557).Although in vitro data implicate sulfonylureas as substrates of organic anion transporting polypeptide 1B1 (OATP1B1) transporter, there is a lack of in vivo data supporting an effect of SLCO1B1 variants on sulfonylurea pharmacokinetics.This contrasts with statins, where the rs4149056 c.521T>C allele is well known to be associated with a 4.6-fold increase in risk of statin-induced myopathy.This is supported by both in vitro evidence of reduced OATP1B1 transporter activity and in vivo pharmacokinetic studies showing higher statin exposure among CC homozygotes (2).Further, Dawed et al. (1) only investigated the role of
Source: Diabetes Care
DOI: 10.2337/dc21-2428
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4220666095