PMID- 37819499 OWN - NLM STAT- MEDLINE DCOM- 20231110 LR - 20240208 IS - 1573-4978 (Electronic) IS - 0301-4851 (Linking) VI - 50 IP - 11 DP - 2023 Nov TI - Role of SLC5A2 polymorphisms and effects of genetic polymorphism on sodium glucose cotransporter 2 inhibitorsinhibitor response. PG - 9637-9647 LID - 10.1007/s11033-023-08836-0 [doi] AB - Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterized by hyperglycaemia. T2DM is a highly heterogeneous polygenic disease. Due to genetic variation, variations in lifestyle and other environmental exposures, there are certain variations in the phenotype of T2DM patients. Sodium glucose cotransporter 2 (SGLT2) inhibitors are novel hypoglycaemic agents that increase urinary glucose excretion by inhibiting glucose reabsorption in the proximal tubules of the kidney. For glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, studies have confirmed a variety of gene variants that may modify their effects. For SGLT2 inhibitors, research has focused on the SLC5A2 gene encoding SGLT2 and UGT1A9 gene polymorphisms affecting SGLT2 inhibitor metabolism. The SLC5A2 polymorphism rs9934336 have been associated with decreased HbA1c during the oral glucose tolerance test. Common variants of the SLC5A2 gene are related to blood glucose and insulin concentrations, but not glucagon concentrations. SLC5A2 rs9934336 and rs3116150 are related to a lower risk of heart failure. SGLT2 inhibitor exposure of UGT1A9*3 carriers is commonly higher than that of noncarriers, while these effects commonly have no obvious clinical significance on SGLT2 inhibitor pharmacokinetics. In terms of efficacy, general SLC5A2 variants show no significant effect on the response to the SGLT2 inhibitor empagliflozin. At present, research on the relationship between genetic polymorphisms and the efficacy of SGLT2 inhibitors is limited. The main purpose of this review is to elucidate the general effects of SGLT2 polymorphisms and the association between polymorphisms and the treatment response to SGLT2 inhibitors. CI - (c) 2023. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Xu, Bo AU - Xu B AD - The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. FAU - Li, Shaoqian AU - Li S AD - The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. FAU - Kang, Bo AU - Kang B AD - The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. FAU - Fan, Shangzhi AU - Fan S AD - The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. FAU - Chen, Canyu AU - Chen C AD - The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. FAU - Li, Weiyi AU - Li W AD - The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. FAU - Chen, Jixiang AU - Chen J AD - The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. FAU - He, Zunbo AU - He Z AD - The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. FAU - Tang, Fan AU - Tang F AD - The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. AD - The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. FAU - Zhou, Jiecan AU - Zhou J AUID- ORCID: 0000-0002-3037-3997 AD - The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. zhoujiecan@fsyy.usc.edu.cn. AD - The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. zhoujiecan@fsyy.usc.edu.cn. AD - The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. zhoujiecan@fsyy.usc.edu.cn. AD - School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. zhoujiecan@fsyy.usc.edu.cn. LA - eng GR - 82003872/NSFC/ GR - 2022JJ50163/Natural Science Foundation of Hunan Province/ GR - 19A418/Scientific research Fund of hunan provincial education department/ GR - 20201973/Scientific Research Fund Project of Hunan Provinci al Health Commission/ GR - 2021QZY016/Central government funds for guiding local scientific and Technological Development/ GR - 2020SK51823/Hunan Province Clinical Medical Technology Innovation Guidance Project/ PT - Journal Article PT - Review DEP - 20231011 PL - Netherlands TA - Mol Biol Rep JT - Molecular biology reports JID - 0403234 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sodium-Glucose Transporter 2) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - IY9XDZ35W2 (Glucose) RN - 0 (SLC5A2 protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Sodium-Glucose Transporter 2/genetics MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Blood Glucose/metabolism MH - Glucose MH - Polymorphism, Genetic/genetics OTO - NOTNLM OT - Polymorphism OT - SLC5A2 OT - Sodium glucose cotransporter 2 inhibitor OT - Type 2 diabetes mellitus EDAT- 2023/10/11 14:42 MHDA- 2023/11/10 06:44 CRDT- 2023/10/11 11:11 PHST- 2023/08/07 00:00 [received] PHST- 2023/09/25 00:00 [accepted] PHST- 2023/11/10 06:44 [medline] PHST- 2023/10/11 14:42 [pubmed] PHST- 2023/10/11 11:11 [entrez] AID - 10.1007/s11033-023-08836-0 [pii] AID - 10.1007/s11033-023-08836-0 [doi] PST - ppublish SO - Mol Biol Rep. 2023 Nov;50(11):9637-9647. doi: 10.1007/s11033-023-08836-0. Epub 2023 Oct 11.