Dabiri R, Mahmoudi T, Sabzikarian M, Asadi A, Farahani H, Nobakht H, Maleki I, Mansour-Ghanaei F, Derakshshan F, Zali M R
Internal Medicine Department, Semnan University of Medical Sciences, Semnan, Iran.
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Acta Gastroenterol Belg. 2020 Apr-Jun;83(2):271-276.
Nonalcoholic fatty liver disease (NAFLD) is an increasing global health concern defined by excessive hepatic fat content in the absence of excessive alcohol consumption. Regarding the key role of insulin and insulin resistance in NAFLD, we investigated whether insulin receptor substrate 1 (IRS1) and insulin receptor substrate 2 (IRS2) gene variants were associated with NAFLD risk.
In this case-control study, 305 subjects including 151 cases with biopsy-proven NAFLD and 154 controls were enrolled. All the subjects were genotyped for IRS1 (rs1801278) and IRS2 (rs2289046) gene variants using PCR-RFLP method.
Our findings showed that the IRS2 rs2289046 "GG+AG" genotype compared with "AA" genotype to be a marker of decreased NAFLD susceptibility and the difference remained significant even after adjustment for confounding factors including age, BMI, sex, smoking status, systolic blood pressure, and diastolic blood pressure (P=0.014; OR=0.50, 95%CI= 0.29-0.87). Furthermore, the IRS2 "G" allele was significantly underrepresented in the cases with NAFLD than controls (P=0.026 ; OR=0.62, 95%CI=0.41-0.94). However, no significant difference was found for IRS1 rs1801278 gene variant.
This study suggests, for the first time, that the IRS2 gene rs2289046 variant may play a role in NAFLD susceptibility. Nevertheless, this observation warrants further investigations in other populations.
非酒精性脂肪性肝病（NAFLD）是一个日益引起全球健康关注的问题，其定义为在无过量饮酒情况下肝脏脂肪含量过高。鉴于胰岛素及胰岛素抵抗在NAFLD中的关键作用，我们研究了胰岛素受体底物1（IRS1）和胰岛素受体底物2（IRS2）基因变异是否与NAFLD风险相关。
在这项病例对照研究中，纳入了305名受试者，其中包括151例经活检证实的NAFLD患者和154名对照。使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对所有受试者的IRS1（rs1801278）和IRS2（rs2289046）基因变异进行基因分型。
我们的研究结果显示，与“AA”基因型相比，IRS2 rs2289046“GG + AG”基因型是NAFLD易感性降低的一个标志物，即使在对包括年龄、体重指数、性别、吸烟状况、收缩压和舒张压等混杂因素进行调整后，差异仍然显著（P = 0.014；比值比[OR]=0.50，95%可信区间[CI]=0.29 - 0.87）。此外，NAFLD患者中IRS2“G”等位基因的比例明显低于对照组（P = 0.026；OR = 0.62，95%CI = 0.41 - 0.94）。然而，未发现IRS1 rs1801278基因变异有显著差异。
本研究首次表明，IRS2基因rs2289046变异可能在NAFLD易感性中起作用。尽管如此，这一观察结果仍需在其他人群中进一步研究。
