NLRP3-Inflammasome Gene Variations in the Risk of Type 2 Diabetes


ÖZBAYER C., KURT H., YAĞCI E., KEBAPÇI M. N., Gunes H. V., DEĞİRMENCİ İ.

Journal of Environmental Pathology, Toxicology and Oncology, vol.41, no.2, pp.1-13, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 41 Issue: 2
  • Publication Date: 2022
  • Doi Number: 10.1615/jenvironpatholtoxicoloncol.2021040001
  • Journal Name: Journal of Environmental Pathology, Toxicology and Oncology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, EMBASE, Environment Index, Greenfile, MEDLINE, Pollution Abstracts
  • Page Numbers: pp.1-13
  • Keywords: genetic variation, inflammasome, NLRP3, type 2 diabetes
  • Kütahya Health Sciences University Affiliated: Yes

Abstract

Inflammation is the natural immunological response of an organism against any harmful, foreign or de-structive effect to heal and repair damaged tissue. The nod-like receptor pyrin domain-containing-3 (NLRP3) inflam-masome is one of the main components of the inflammatory mechanism and is associated with many inflammatory diseases, but it is also closely related to metabolic abnormalities, such as type 2 diabetes mellitus (T2DM), insulin resistance and obesity. NLRP3 activates inflammation and causes interleukin-1β release, exogenous and endogenous danger signals, as well as insulin resistance. In this direction, we focus on the gene structure of NLRP3 in diabetes and accordingly, we aim to determine the relationship between eight gene variations in the NLRP3 gene and T2DM. We investigated the rs10802501, rs10733113, rs10754558, rs10925026, rs10925027, rs35829419, rs4612666 and rs4925659 single-nucleotide polymorphisms of NLRP3 gene using the Sequenom MassARRAY system in 100 T2DM patients and 100 control individuals. There were no significant differences between T2DM risk and the genotype frequencies of rs10802501, rs10733113, rs35829419 and rs10925026 variants (p > 0.05). However, significant genotype frequencies were determined for rs10925027 (p = 0.0013) and rs4925659 (p < 0.001). For the risk allele G of the rs10754558 vari-ant, significant differences were found in the heterozygous and dominant model (p = 0.036, p = 0.033). The genotype distribution of the rs4612666 variant was significant only in the heterozygous model (p = 0.047). In this hospital-based case-control study, rs10925027, rs4925659 and rs10754558 variants were found to be closely related to T2DM risk. The rs10925027 CC genotype, rs4925659 GG genotype, rs10754558 GG and GC+GG genotypes of the NLRP3 were determined as important risk factors for the T2DM.