Molecular investigation of the effects of interleukin-6 (IL-6) and uridine 5'-diphospho-glucuronyltransferase 1 (UGT1A1) mutations on the formation of heart failure and diuretic resistance

Furosemide is a diuretic and is used for treatment of patients with heart failure. It has been found that in some patients, the drug does not work in sufficient quantities. This condition is named as furosemide resistance. In this study, it is aimed to investigate the relationship between UGT1A1 and IL-6 mutations with furosemide resistance in patients with heart failure. Sixty heart failure patients using furosemide (patient group) and 30 healthy individuals (control group) were enrolled in this study. Patients were divided into 2 subgroups as furosemide resistant (non-responders) group (n=30) and the non-resistant (responders) group (n=30). Mutations in the first exon of UGT1A1; rs1800795 and rs1800796 mutations in IL-6 were analyzed by direct sequencing and real-time polymerase chain reaction (RT-PCR), respectively. At the end of the study, eleven mutations were detected in UGT1A1, of which nine of them are novel. Also, rs1800795 and rs1800796 mutations were detected in all of 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 patient and control groups, the C allele of rs1800796 mutation in IL-6 was found statistically high in the patient group (p=0,032). When allele distributions were compared between the three groups, 55 T-insertion in UGT1A1 was found statistically high in the non-responders group (p=0,017). Three mutations were found deleterious and six mutations were detected as probably damaging to protein functions. It is thought that our study will contribute to the elucidation of pharmacogenetic features (drug response-gene relationship) and the development of individual-specific treatment strategies in heart failure patients using furosemide.