Amir Amna, Hussain Sabir, Shah Syed Tahir Abbas, Habib Rabia, Muneer Zahid, Nepovimova Eugenie, Kuca Kamil, Nurulain Syed Muhammad
Department of Biosciences, COMSATS University Islamabad, Park Road Tarlai, Islamabad, 45550, Pakistan.
Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62,500 03, Hradec Kraloveit, Hradec Kralove, Czech Republic.
Int J Obes (Lond). 2025 May;49(5):881-887. doi: 10.1038/s41366-025-01715-7. Epub 2025 Jan 28.
Obesity plays a crucial role in the development of metabolic disorders including diabetes, coronary and renal diseases. There are several factors involved in the pathology of obesity, including chronic inflammation and exposure to environmental contaminants. Recently, the cholinergic co-hydrolyzing enzyme BChE has been associated with clinical conditions such as diabetes and obesity. This study aims to investigate the levels of BChE and inflammatory markers in the serum, as well as the association between two specific BCHE gene variants (rs1803274 and rs3495) and the risk of obesity in the Pakistani population.
The study recruited 350 people with obesity and 200 volunteers with no obesity. Proinflammatory cytokines (TNF-α, IL-6, and IL-1β) levels were quantified using ELISA kits, while the analysis of BCHE gene SNPs rs1803274 (K-variant) and rs3495 was conducted using the tetra-primer amplification refractory mutation-PCR (tetra-ARM-PCR) and PCR-restriction fragment length polymorphism (RFLP) methods, respectively. Additionally, clinico-pathological parameters HDL, LDL, BMI, Homa-IR, insulin, glucose, blood pressure was also assessed in subjects of current study.
Results showed significantly higher levels of BChE, TNF-α, IL-1β, and IL-6 in the obesity group compared to the group without obesity. Furthermore, the obesity group exhibited higher blood pressure and LDL levels, as well as lower HDL levels when compared to group without obesity. Logistic regression analysis revealed a relationship between obesity and higher BChE activity, blood pressure, LDL, and lower HDL levels. The study also found a statistically significant association between the BCHE gene SNPs rs1803274 (K-variant) and rs3495 and the risk of obesity (OR = 2.01; CI = 1.21-3.33; p = 0.0063; OR = 1.80; CI = 1.09-2.96, respectively).
In conclusion, the study suggests that BChE and inflammatory cytokines play a significant role in the development and pathogenesis of obesity and can also act as good diagnostic biomarkers for obesity and its related metabolic disorders.
肥胖在包括糖尿病、心血管疾病和肾脏疾病在内的代谢紊乱发展过程中起着关键作用。肥胖的病理过程涉及多种因素,包括慢性炎症和接触环境污染物。最近,胆碱能共水解酶丁酰胆碱酯酶(BChE)已与糖尿病和肥胖等临床病症相关联。本研究旨在调查巴基斯坦人群血清中BChE和炎症标志物的水平,以及两种特定的BCHE基因变体(rs1803274和rs3495)与肥胖风险之间的关联。
该研究招募了350名肥胖者和200名非肥胖志愿者。使用酶联免疫吸附测定(ELISA)试剂盒对促炎细胞因子(肿瘤坏死因子-α、白细胞介素-6和白细胞介素-1β)水平进行定量,而分别使用四引物扩增阻滞突变PCR(tetra-ARM-PCR)和聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对BCHE基因单核苷酸多态性rs1803274(K变体)和rs3495进行分析。此外,还对本研究对象的临床病理参数高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、体重指数(BMI)、胰岛素抵抗指数(Homa-IR)、胰岛素、血糖、血压进行了评估。
结果显示,与非肥胖组相比,肥胖组的BChE、肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6水平显著更高。此外,与非肥胖组相比,肥胖组的血压和LDL水平更高,而HDL水平更低。逻辑回归分析显示肥胖与更高的BChE活性、血压、LDL以及更低的HDL水平之间存在关联。该研究还发现BCHE基因单核苷酸多态性rs1803274(K变体)和rs3495与肥胖风险之间存在统计学上的显著关联(比值比分别为2.01;置信区间为1.21 - 3.33;p = 0.0063;比值比为1.80;置信区间为1.09 - 2.96)。
总之,该研究表明BChE和炎症细胞因子在肥胖的发生和发病机制中起重要作用,并且还可作为肥胖及其相关代谢紊乱的良好诊断生物标志物。