Il-6 and UGT1A1 variations may related to furosemide resistance in heart failure patients.

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Contributed Indexing:	Keywords: IL-6; UGT1A1; diuretic resistance; furosemide; heart failure
Substance Nomenclature:	7LXU5N7ZO5 (Furosemide) 0 (Interleukin-6) EC 2.4.1.17 (Glucuronosyltransferase) 0 (Diuretics)
Entry Date(s):	Date Created: 20230601 Date Completed: 20230914 Latest Revision: 20230914
Update Code:	20230914
DOI:	10.1002/iub.2732
PMID:	37260062
Autor:	Koprululu Kucuk G; Faculty of Medicine, Department of Medical Biology, Yeditepe University, Istanbul, Turkey.; Department of Radiotherapy, Istanbul Sisli Vocational School, Istanbul, Turkey., Guney AI; Faculty of Medicine, Department of Medical Genetics, Marmara University, Istanbul, Turkey., Sunbul M; Faculty of Medicine, Department of Cardiology, Marmara University, Istanbul, Turkey., Guctekin T; Faculty of Medicine, Department of Cardiology, Marmara University, Istanbul, Turkey., Koç G; Faculty of Medicine, Department of Medical Biology, Istanbul Aydın University, Istanbul, Turkey., Kirac D; Faculty of Medicine, Department of Medical Biology, Yeditepe University, Istanbul, Turkey.
Jazyk:	angličtina
Zdroj:	IUBMB life [IUBMB Life] 2023 Oct; Vol. 75 (10), pp. 830-843. Date of Electronic Publication: 2023 Jun 01.
DOI:	10.1002/iub.2732
Abstrakt:	Furosemide is a diuretic and is used for the treatment of patients with heart failure (HF). It has been found that in some HF patients, the drug does not treat patients efficiently. This condition is named as furosemide resistance. In this study, it is aimed to investigate the relationship between UDP-glucuronosyltransferase 1 (UGT1A1) and interleukine-6 (IL-6) variations with furosemide resistance in HF patients. Sixty HF patients using furosemide (patient group) and 30 healthy individuals (control group) were enrolled in this study. Patients were divided into two subgroups as non-responders (furosemide resistant) group (n = 30) and the responders (non-resistant) group (n = 30) according to the presence of furosemide resistance (n = 30). Variations in the first exon of UGT1A1 and rs1800795 and rs1800796 variations in IL-6 were analyzed by direct sequencing and real-time polymerase chain reaction (RT-PCR), respectively. The effects of newly detected mutations on 3-D protein structure were analyzed by in silico analysis. At the end of the study, 11 variations were detected in UGT1A1, of which nine of them are novel and eight of them cause amino acid change. Also, rs1800795 and rs1800796 variations were detected in all the groups. When patient and control groups were compared with each other, rs1800796 mutation in IL-6 was found statistically high in the patient group (p = 0.027). When the three groups were compared with each other, similarly, rs1800796 mutation in IL-6 was found statistically high in the non-responders group (p = 0.043). When allele distributions were compared between the patient and control groups, the C allele of rs1800795 mutation in IL-6 was found statistically high in the patient group (p = 0.032). When allele distributions were compared between the three groups, 55T-insertion in UGT1A1 was found statistically high in the non-responders group (p = 0.017). According to in silico analysis results, two variations were found deleterious and six variations were detected as probably damaging to protein functions. Our study may contribute to the elucidation of pharmacogenetic features (drug response-gene relationship) and the development of individual-specific treatment strategies in HF patients using furosemide. (© 2023 International Union of Biochemistry and Molecular Biology.)
Databáze:	MEDLINE
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