Association between insulin-associated gene polymorphisms and new-onset diabetes mellitus in statin-treated patients
Minju Park
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Search for more papers by this authorJung Sun Kim
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Search for more papers by this authorYoon-A Park
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Search for more papers by this authorDa Hoon Lee
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Search for more papers by this authorSeo-A Choi
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Search for more papers by this authorYoonkyung Chang
Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea
Search for more papers by this authorCorresponding Author
Tae-Jin Song
Department of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, South Korea
Correspondence
Tae-Jin Song, Department of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, 260 Gonghang-daero, Gangseo-gu, Seoul 07804, South Korea.
Email: [email protected]
Hye Sun Gwak, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, South Korea.
Email: [email protected]
Jeong Yee, School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, South Korea.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Hye Sun Gwak
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Correspondence
Tae-Jin Song, Department of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, 260 Gonghang-daero, Gangseo-gu, Seoul 07804, South Korea.
Email: [email protected]
Hye Sun Gwak, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, South Korea.
Email: [email protected]
Jeong Yee, School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, South Korea.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Jeong Yee
School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
Correspondence
Tae-Jin Song, Department of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, 260 Gonghang-daero, Gangseo-gu, Seoul 07804, South Korea.
Email: [email protected]
Hye Sun Gwak, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, South Korea.
Email: [email protected]
Jeong Yee, School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, South Korea.
Email: [email protected]
Search for more papers by this authorMinju Park
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Search for more papers by this authorJung Sun Kim
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Search for more papers by this authorYoon-A Park
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Search for more papers by this authorDa Hoon Lee
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Search for more papers by this authorSeo-A Choi
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Search for more papers by this authorYoonkyung Chang
Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea
Search for more papers by this authorCorresponding Author
Tae-Jin Song
Department of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul, South Korea
Correspondence
Tae-Jin Song, Department of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, 260 Gonghang-daero, Gangseo-gu, Seoul 07804, South Korea.
Email: [email protected]
Hye Sun Gwak, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, South Korea.
Email: [email protected]
Jeong Yee, School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, South Korea.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Hye Sun Gwak
College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea
Correspondence
Tae-Jin Song, Department of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, 260 Gonghang-daero, Gangseo-gu, Seoul 07804, South Korea.
Email: [email protected]
Hye Sun Gwak, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, South Korea.
Email: [email protected]
Jeong Yee, School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, South Korea.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Jeong Yee
School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
Correspondence
Tae-Jin Song, Department of Neurology, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, 260 Gonghang-daero, Gangseo-gu, Seoul 07804, South Korea.
Email: [email protected]
Hye Sun Gwak, College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, South Korea.
Email: [email protected]
Jeong Yee, School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon 16419, South Korea.
Email: [email protected]
Search for more papers by this authorMinju Park and Jung Sun Kim contributed equally to this work.
Abstract
Background
While statins are effective at managing lipid levels, there is growing evidence for new-onset diabetes mellitus (NODM). The insulin signalling pathway (ISP) inhibited by statins is one of the potential mechanisms; however, most studies have been limited to in vitro settings. Therefore, this study aimed to identify the genetic associations within the ISP-related genes and NODM.
Methods
We performed a retrospective analysis of samples collected prospectively from February 2021 to May 2021. Among ISP-related genes, we selected 11 candidate genes (IGF1, IGF2, IGF1R, INSR, IRS1, IRS2, PIK3CA, PIK3CB, PIK3R1, AKT1 and AKT2). An additional analysis was conducted comparing patients with DM prior to statin therapy and controls to determine whether the single nucleotide polymorphisms (SNPs) are specific to statin.
Results
A total of 602 patients were analysed, including 71 (11.8%) with statin-induced NODM. After adjustment, IGF1R rs2715439, INSR rs1799817, INSR rs2059807 and PIK3R1 rs3730089 were found to be independently associated with NODM. In an additional analysis, all SNPs that demonstrated an association with statin-induced NODM lost their significance in patients with DM prior to statin therapy.
Conclusion
This study revealed the ISP-related genetic effects, specifically involving genes such as INSR, IGF1R and PIK3R1, in the development of statin-induced NODM. Our findings suggest a potential mechanism of statin-induced NODM related to ISP-related genetic variants.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
Supporting Information
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| eci14366-sup-0001-Supinfo.docxWord 2007 document , 53.5 KB |
Data S1. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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