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Licensed Unlicensed Requires Authentication Published online by De Gruyter June 24, 2022

Type 2 diabetes: an exploratory genetic association analysis of selected metabolizing enzymes and transporters and effects on cardiovascular and renal biomarkers

Russell W. Fankhouser, Derek E. Murrell, Yaa Y. Anane, David L. Hurley, Hadii M. Mamudu and Sam Harirforoosh ORCID logo

Abstract

Objectives

This study sought to identify potential pharmacogenetic associations of selected enzymes and transporters with type 2 diabetes (T2D). In addition, pharmacogenomic profiles, concentrations of asymmetric dimethylarginine (ADMA) or kidney injury molecule-1 (KIM-1), and several covariates were investigated.

Methods

Whole blood was collected from 63 patients, with 32 individuals with T2D. A pharmacogenomic panel was used to assay genetic profiles, and biomarker ELISAs were run to determine subject concentrations of ADMA and KIM-1. Additive genetic modeling with multiple linear and logistic regressions were performed to discover potential SNPs-outcome associations using PLINK.

Results

Ten SNPs were found to be significant (p<0.05) depending on the inclusion or exclusion of covariates. Of these, four were found in association with the presence of T2D, rs2231142, rs1801280, rs1799929, and rs1801265 depending on covariate inclusion or exclusion. Regarding ADMA, one SNP was found to be significant without covariates, rs1048943. Five SNPs were identified in association with KIM-1 and T2D in the presence of covariates, rs12208357, rs34059508, rs1058930, rs1902023, and rs3745274. Biomarker concentrations were not significantly different in the presence of T2D.

Conclusions

This exploratory study found several SNPs related to T2D; further research is required to validate and understand these relationships.


Corresponding author: Dr. Sam Harirforoosh, Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Box 70594, Johnson City, TN 37614-1708, USA, Fax: +1 423 439 6350, E-mail:
Russell W. Fankhouser and Derek E. Murrell contributed equally to this work.

Funding source: East Tennessee State University

Award Identifier / Grant number: Unassigned

  1. Research funding: We would like to thank Dr. Peter Panus for his assistance with statistical analysis. This study was funded in part by a Research and Development Committee Interdisciplinary Grant from East Tennessee State University.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: The local Institutional Review Board deemed the study exempt from review.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/dmpt-2021-0135).


Received: 2021-04-28
Accepted: 2022-03-14
Published Online: 2022-06-24

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