Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes.
SNP
T2DM
cardiovascular death
metformin
organic cation transporter 1
Journal
Diabetes, metabolic syndrome and obesity : targets and therapy
ISSN: 1178-7007
Titre abrégé: Diabetes Metab Syndr Obes
Pays: New Zealand
ID NLM: 101515585
Informations de publication
Date de publication:
2020
2020
Historique:
received:
22
10
2019
accepted:
01
05
2020
entrez:
2
7
2020
pubmed:
2
7
2020
medline:
2
7
2020
Statut:
epublish
Résumé
Organic cation transporters (Octs) use cations like endogenous compounds, toxins, and drugs, such as metformin, as substrates. Therefore, these proteins determine the pharmacokinetics and -dynamics of metformin and thus its efficacy. Of note, metformin is today the most commonly used pharmaceutical in the treatment of type 2 diabetes (T2DM) with nevertheless a great variability in clinical response, which attributes to genetic variances. The aim of this study was to determine the influence of intronic OCT1 SNPs on prevalence of all-cause and cardiovascular death. Genotypes of 27 intronic SNPs in OCT1 were investigated in the LURIC study, a prospective cohort of 3316 participants scheduled for coronary angiography. We investigated whether these variants were associated with all-cause and cardiovascular death in 73 individuals with T2DM under metformin therapy, in individuals without diabetes, individuals with T2DM and individuals with T2DM without metformin therapy. In a multivariate Cox regression analysis adjusted for classical cardiovascular risk factors, 4 intronic OCT1 SNPs were significantly associated with all-cause and cardiovascular mortality in individuals with T2DM on metformin therapy. According to their OCT1 genotype, some individuals with T2DM on metformin therapy might be prone to an increased risk of cardiovascular death.
Identifiants
pubmed: 32606866
doi: 10.2147/DMSO.S235663
pii: 235663
pmc: PMC7308180
doi:
Types de publication
Journal Article
Langues
eng
Pagination
2069-2080Informations de copyright
© 2020 Schweighofer et al.
Déclaration de conflit d'intérêts
Dr Natascha Schweighofer reports grants from the Austrian Federal Government within the COMET K1 Centre Program, Land Steiermark and Land Wien, during the conduct of the study; and she is an employee in CBmed GmbH, Center for Biomarker Research in Medicine, outside the submitted work. Dr Marcus E Kleber reports personal fees from Bayer, outside the submitted work. Prof. Dr. Thomas R Pieber reports grants, personal fees from AstraZeneca, grants, personal fees from Novo Nordisk, personal fees from Adocia, personal fees from Arecor, personal fees from Sanofi, personal fees from Roche Diagnostics, outside the submitted work. The authors report no other conflicts of interest in this work.
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