nlrp3 -炎性小体基因变异与2型糖尿病的风险

C. Ozbayer, H. Kurt, Emine Yagci, M. Kebapçı, H. Gunes, I. Degirmenci
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引用次数: 3

摘要

炎症是机体对任何有害、外来或破坏性影响的自然免疫反应,目的是愈合和修复受损组织。淋巴结样受体pyrin结构域-3 (NLRP3)炎症小体是炎症机制的主要组成部分之一,与许多炎症性疾病有关,但它也与代谢异常密切相关,如2型糖尿病(T2DM)、胰岛素抵抗和肥胖。NLRP3激活炎症,引起白细胞介素-1β释放,外源性和内源性危险信号,以及胰岛素抵抗。在这个方向上,我们将重点研究NLRP3在糖尿病中的基因结构,从而确定NLRP3基因的8个基因变异与T2DM的关系。采用Sequenom MassARRAY系统对100例T2DM患者和100例对照进行NLRP3基因rs10802501、rs10733113、rs10754558、rs10925026、rs10925027、rs35829419、rs4612666和rs4925659单核苷酸多态性研究。rs10802501、rs10733113、rs35829419、rs10925026变异基因型频率与T2DM风险无显著差异(p > 0.05)。然而,rs10925027 (p = 0.0013)和rs4925659 (p < 0.001)的基因型频率显著。rs10754558变异的风险等位基因G在杂合模型和显性模型中存在显著差异(p = 0.036, p = 0.033)。rs4612666变异的基因型分布仅在杂合模式下显著(p = 0.047)。在这项以医院为基础的病例对照研究中,发现rs10925027、rs4925659和rs10754558变异与T2DM风险密切相关。NLRP3的rs10925027 CC基因型、rs4925659 GG基因型、rs10754558 GG和GC+GG基因型被确定为T2DM的重要危险因素。
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NLRP3-Inflammasome Gene Variations in the Risk of Type 2 Diabetes.
Inflammation is the natural immunological response of an organism against any harmful, foreign or destructive effect to heal and repair damaged tissue. The nod-like receptor pyrin domain-containing-3 (NLRP3) inflammasome 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 variant, 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.
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