Kempinska-Podhorodecka Agnieszka, Wunsch Ewa, Milkiewicz Piotr, Stachowska Ewa, Milkiewicz Malgorzata
Department of Medical Biology, Pomeranian Medical University, 70-111 Szczecin, Poland.
Translational Medicine Group, Pomeranian Medical University, 71-210 Szczecin, Poland.
J Clin Med. 2019 Nov 8;8(11):1912. doi: 10.3390/jcm8111912.
Suppressor of cytokine signaling (SOCS) proteins prevent uncontrolled cytokine signaling and appear to play a role in the pathological processes behind obesity and insulin resistance. The polymorphism of the gene (rs243330, -1656G>A) is associated with obesity and glucose sensitivity. To estimate the effect of this gene polymorphism on nonalcoholic fatty liver disease (NAFLD) susceptibility, we performed a study on 138 patients with ultrasound-confirmed NAFLD and 1000 healthy blood donors. The relationship between the SOCS1-1656G>A polymorphism and serum biochemical parameters in NAFLD was additionally investigated. The variant was genotyped using a dedicated TaqMan assay. The frequency of rs243330 polymorphism did not differ between patients and controls. However, in a cohort of obese individuals (BMI ≥ 30 kg/m) the occurrence of the G allele of the SOCS1-1656G>A polymorphism was strongly associated with NAFLD (odds ratio (OR) 1.6; 95% CI,1.1-2.5; = 0.009), and carriers of the AA genotype have lower risk of developing NAFLD (OR 0.4; 95% CI, 0.2-0.7; = 0.004). Overweight NAFLD patients who were carriers of GG genotypes had significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) values ( = 0.03 vs. AA), and the obese GG homozygotes had lower serum concertation of triglyceride (GG vs. AA; = 0.02). Serum liver enzyme activities were not modified by the presence of risk variants. In conclusion, the observed phenotype of overweight NAFLD patients with non-elevated levels of TG and HOMA-IR, which is associated with genetic variants of , provides a rationale for further research on the pathophysiology of fatty liver disease.
细胞因子信号转导抑制因子（SOCS）蛋白可防止细胞因子信号不受控制，并似乎在肥胖和胰岛素抵抗背后的病理过程中发挥作用。该基因（rs243330，-1656G>A）的多态性与肥胖和葡萄糖敏感性相关。为了评估这种基因多态性对非酒精性脂肪性肝病（NAFLD）易感性的影响，我们对138例经超声确诊的NAFLD患者和1000名健康献血者进行了一项研究。此外，还研究了SOCS1-1656G>A多态性与NAFLD患者血清生化参数之间的关系。使用专用的TaqMan分析对该变体进行基因分型。rs243330多态性的频率在患者和对照组之间没有差异。然而，在肥胖个体（BMI≥30kg/m）队列中，SOCS1-1656G>A多态性的G等位基因的出现与NAFLD密切相关（优势比（OR）1.6；95%可信区间，1.1-2.5；P=0.009），AA基因型携带者患NAFLD的风险较低（OR 0.4；95%可信区间，0.2-0.7；P=0.004）。携带GG基因型的超重NAFLD患者的胰岛素抵抗稳态模型评估（HOMA-IR）值显著较低（与AA相比，P=0.03），肥胖的GG纯合子的甘油三酯血清浓度较低（GG与AA相比；P=0.02）。血清肝酶活性不受风险变体存在的影响。总之，观察到的TG和HOMA-IR水平未升高的超重NAFLD患者的表型与该基因的遗传变体相关，这为进一步研究脂肪性肝病的病理生理学提供了理论依据。
