Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes

Natascha Schweighofer,1,2 Bernd Genser,3,4 Winfried Maerz,5,6 Marcus E Kleber,5 Olivia Trummer,1 Thomas R Pieber,1,2 Barbara Obermayer-Pietsch1,2 1Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Graz, Austria; 2CBmed GmbH, Center for Biomarker Res...

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Autores principales:	Schweighofer N, Genser B, Maerz W, Kleber ME, Trummer O, Pieber TR, Obermayer-Pietsch B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	organic cation transporter 1 snp t2dm cardiovascular death metformin Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/0aeeac38813d4534af99c797be7e153b
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spelling	oai:doaj.org-article:0aeeac38813d4534af99c797be7e153b2021-12-02T10:37:32ZIntronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes1178-7007https://doaj.org/article/0aeeac38813d4534af99c797be7e153b2020-06-01T00:00:00Zhttps://www.dovepress.com/intronic-variants-in-oct1-are-associated-with-all-cause-and-cardiovasc-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Natascha Schweighofer,1,2 Bernd Genser,3,4 Winfried Maerz,5,6 Marcus E Kleber,5 Olivia Trummer,1 Thomas R Pieber,1,2 Barbara Obermayer-Pietsch1,2 1Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Graz, Austria; 2CBmed GmbH, Center for Biomarker Research in Medicine, Graz, Austria; 3BG Stats Consulting, Vienna, Austria; 4Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany; 5Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; 6SynLaboratory Academy, SynLaboratory Holding Deutschland GmbH, Mannheim and Augsburg, GermanyCorrespondence: Barbara Obermayer-PietschDepartment of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Auenbruggerplatz 15, Graz A-8036, AustriaTel +43 316 385 80253Fax +43 316 385 13428Email barbara.obermayer@medunigraz.atPurpose: 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.Patients and Methods: 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.Results: 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.Conclusion: According to their OCT1 genotype, some individuals with T2DM on metformin therapy might be prone to an increased risk of cardiovascular death.Keywords: organic cation transporter 1, SNP, T2DM, cardiovascular death, metforminSchweighofer NGenser BMaerz WKleber METrummer OPieber TRObermayer-Pietsch BDove Medical Pressarticleorganic cation transporter 1snpt2dmcardiovascular deathmetforminSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 2069-2080 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	organic cation transporter 1 snp t2dm cardiovascular death metformin Specialties of internal medicine RC581-951
spellingShingle	organic cation transporter 1 snp t2dm cardiovascular death metformin Specialties of internal medicine RC581-951 Schweighofer N Genser B Maerz W Kleber ME Trummer O Pieber TR Obermayer-Pietsch B Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes
description	Natascha Schweighofer,1,2 Bernd Genser,3,4 Winfried Maerz,5,6 Marcus E Kleber,5 Olivia Trummer,1 Thomas R Pieber,1,2 Barbara Obermayer-Pietsch1,2 1Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Graz, Austria; 2CBmed GmbH, Center for Biomarker Research in Medicine, Graz, Austria; 3BG Stats Consulting, Vienna, Austria; 4Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany; 5Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; 6SynLaboratory Academy, SynLaboratory Holding Deutschland GmbH, Mannheim and Augsburg, GermanyCorrespondence: Barbara Obermayer-PietschDepartment of Internal Medicine, Division of Endocrinology and Diabetology, Medical University Graz, Auenbruggerplatz 15, Graz A-8036, AustriaTel +43 316 385 80253Fax +43 316 385 13428Email barbara.obermayer@medunigraz.atPurpose: 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.Patients and Methods: 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.Results: 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.Conclusion: According to their OCT1 genotype, some individuals with T2DM on metformin therapy might be prone to an increased risk of cardiovascular death.Keywords: organic cation transporter 1, SNP, T2DM, cardiovascular death, metformin
format	article
author	Schweighofer N Genser B Maerz W Kleber ME Trummer O Pieber TR Obermayer-Pietsch B
author_facet	Schweighofer N Genser B Maerz W Kleber ME Trummer O Pieber TR Obermayer-Pietsch B
author_sort	Schweighofer N
title	Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes
title_short	Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes
title_full	Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes
title_fullStr	Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes
title_full_unstemmed	Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes
title_sort	intronic variants in oct1 are associated with all-cause and cardiovascular mortality in metformin users with type 2 diabetes
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/0aeeac38813d4534af99c797be7e153b
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Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes

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