한빛사논문
- 조회356
Chung, Sung Won1,2; Moon, Hye-Sung3; Shin, Hyunjae1; Han, Hyein4; Park, Sehoon5; Cho, Heejin1; Park, Jeayeon1; Hur, Moon Haeng1; Park, Min Kyung1; Won, Sung-Ho3,4,6,7; Bin Lee, Yun1; Cho, Eun Ju1; Yu, Su Jong1; Kim, Dong Ki5; Yoon, Jung-Hwan1; Lee, Jeong-Hoon1,8; Kim, Yoon Jun1
1Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
2Division of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
3RexSoft Inc., Seoul, South Korea
4Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, South Korea
5Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
6Interdisciplinary Program for Bioinformatics, College of Natural Science, Seoul National University, Seoul, South Korea
7Institute of Health and Environment, Seoul National University, Seoul, South Korea
8Genome Insight Inc., San Diego, CA
Sung Won Chung, Hye-Sung Moon, Hyunjae Shin : These three authors equally contributed as co-first authors
Jeong-Hoon Lee, Yoon Jun Kim These : two authors equally contributed as co-corresponding authors
Correspondence Yoon Jun Kim, Jeong-Hoon Lee
Abstract
Background aims: No medication has been found to reduce the liver-related events. We evaluated the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2i) on liver-related outcomes.
Approach results: Single nucleotide polymorphisms (SNPs) associated with SGLT2 inhibition were identified, and a genetic risk score (GRS) was computed using the UK Biobank (UKB) data (n=337,138). Two-sample Mendelian randomization (MR) was conducted using the FinnGen (n=218,792) database and UKB data. In parallel, a nationwide population-based study using the Korean National Health Insurance Service (NHIS) database was conducted. The development of liver-related complications (i.e., hepatic decompensation, hepatocellular carcinoma, liver transplantation, and death) was compared between individuals with type 2 diabetes mellitus and steatotic liver diseases treated with SGLT2i (n=13,208) and propensity score-matched individuals treated with dipeptidyl peptidase-4 inhibitor (DPP4i) (n=70,342). After computing GRS with six SNPs (rs4488457, rs8057326, rs11865835, rs9930811, rs34497199, and rs35445454), GRS-based MR showed that SGLT2 inhibition (per 1 SD increase of GRS, 0.1% lowering of HbA1c) was negatively associated with cirrhosis development (adjusted odds ratio=0.83, 95% confidence interval [CI]=0.70-0.98, p=0.03) and this was consistent in two-sample MR (odds ratio=0.73, 95% CI=0.60-0.90, p=0.003). In the Korean NHIS database, the risk of liver-related complications was significantly lower in the SGLT2i group than in the DPP4i group (adjusted hazard ratio [aHR]=0.88, 95% CI=0.79-0.97, p=0.01), and this difference remained significant (aHR=0.72-0.89, all p<0.05) across various sensitivity analyses.
Conclusions: Both Mendelian randomizations using two European cohorts and a Korean nationwide population-based cohort study suggest that SGLT2 inhibition is associated with a lower risk of liver-related events.
논문정보
- Research article
- 2024년 03월 (BRIC 등록일 2024-03-12)
- 국내(교신)+국외 연구진
- 의약학 > 응용의학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
