Abdollahi Samira, Lotfi Abbas Sahebghadam, Saravani Ramin, Taheri Hamed
Department of Clinical Biochemistry, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
Biochem Biophys Rep. 2025 Mar 18;42:101974. doi: 10.1016/j.bbrep.2025.101974. eCollection 2025 Jun.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a type of fat accumulation in the liver that can lead to cirrhosis and chronic liver disease. MASLD is recognized as the most frequent of liver-associated deaths worldwide. The gene encodes a serine protease protein that plays a pivotal role in the pathogenesis of liver deficiencies. In this study, we aimed to evaluate the genetic association between rs6647 (M1), rs709932 (M2), and rs1303 (M3) variants in the gene and the risk of MASLD in an Iranian population.
In this case-control study, 120 patients affected by MASLD and 120 healthy subjects participated. The Nephelometry system measured serum levels of α1-antitrypsin (A1AT). Biochemical tests were conducted to assess serum levels of blood parameters using commercially available kits. DNA extraction was performed using the salting-out method, followed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method for genotyping. Statistical analysis was performed by SPSS v16.0.
The findings showed that the rs6647 G allele significantly increased the risk of MASLD. The G allele in codominant, dominant, and over-dominant models caused an increase in the risk of MASLD. Additionally, the rs709932 T allele was more frequent among patients compared to healthy subjects and significantly enhanced the risk of MASLD. The T allele in the codominant and recessive models indicated a high risk for MASLD in our population. The G allele of rs1303 caused an enhancement in the mean serum levels of A1AT in the MASLD group.
Our results show an association between gene variants and the risk of MASLD. The rs6647 (M1) and rs709932 (M2) variants of the gene increased the risk of disorder in our population.
代谢功能障碍相关脂肪性肝病（MASLD）是一种肝脏脂肪堆积疾病，可导致肝硬化和慢性肝病。MASLD被认为是全球与肝脏相关死亡的最常见原因。该基因编码一种丝氨酸蛋白酶蛋白，在肝脏缺陷的发病机制中起关键作用。在本研究中，我们旨在评估该基因中rs6647（M1）、rs709932（M2）和rs1303（M3）变异与伊朗人群中MASLD风险之间的遗传关联。
在这项病例对照研究中，120名受MASLD影响的患者和120名健康受试者参与其中。散射比浊法系统测量血清α1-抗胰蛋白酶（A1AT）水平。使用市售试剂盒进行生化检测以评估血液参数的血清水平。采用盐析法进行DNA提取，随后采用扩增阻滞突变系统-聚合酶链反应（ARMS-PCR）方法进行基因分型。使用SPSS v16.0进行统计分析。
研究结果表明，rs6647的G等位基因显著增加了MASLD的风险。共显性、显性和超显性模型中的G等位基因导致MASLD风险增加。此外，与健康受试者相比，rs709932的T等位基因在患者中更为常见，并显著增加了MASLD的风险。共显性和隐性模型中的T等位基因表明我们人群中MASLD的风险较高。rs1303的G等位基因导致MASLD组中A1AT的平均血清水平升高。
我们的结果表明该基因变异与MASLD风险之间存在关联。该基因的rs6647（M1）和rs709932（M2）变异增加了我们人群中疾病的风险。
