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ACAT1 rs10913733基因多态性与非酒精性脂肪性肝病发病风险的相关性研究
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Abstract:
目的:在中国青岛地区人群中,探讨ACAT1 rs10913733位点基因多态性与非酒精性脂肪性肝病发病风险的相关性。方法:随机纳入2022年06月~2023年06月就诊于青岛市市立医院的289名不同性别、年龄的受试者,其中NAFLD患者197人、健康对照者92人。采集受试者一般临床资料,并检测血液生化学指标。采用PCR以及MALDI-TOF质谱分析技术检测ACAT1 rs10913733基因型。采用SPSS 26.0软件进行统计学分析。结果:ACAT1 rs10913733位点基因型(GG, GT, TT)及等位基因分布在NAFLD组和健康对照组之间无明显差异(P > 0.05)。应用非条件logistics回归分析显示,ACAT1 rs10913733位点基因型及等位基因分布频率与NAFLD发病风险无相关性(P > 0.05)。在所有受试者及NAFLD组患者中,T等位基因非携带者有着更高的TC水平(P < 0.05)。结论:在中国青岛部分人群中,ACAT1 rs10913733多态性与NAFLD发病风险无显著相关性。在所有受试者及NAFLD组中ACAT1 rs10913733的T等位基因非携带均与血胆固醇水平升高有关。
Objective: To investigate the relationship between the gene polymorphism of ACAT1rs109137 at position 33 and the risk of non-alcoholic fatty liver disease (NAFLD) in a population in Qingdao, China. Methods: A total of 289 subjects of different genders and ages were randomly enrolled from June 2022 to June 2023 at the Qingdao Municipal Hospital. Among them, 197 were NAFLD patients and 92 were healthy controls. All subjects’ general clinical data were collected, and blood biochemical indicators were measured. Total DNA was extracted, and the ACAT1 rs109137 polymorphism was detected by PCR and MALDI-TOF mass spectrometry. Statistical analyses were conducted using SPSS 26.0 software. Results: There was no significant difference in the genotype and allele frequency of the ACAT1 rs10913733 locus (GG, GT, and TT) between the NAFLD group and the healthy control group (P > 0.05). Non-conditional logistic regression analysis showed that the ACAT1 rs10913733 locus genotype and allele frequency were not associated with the risk of NAFLD (P > 0.05). In all subjects and NAFLD patients, T allele non-carriers had higher TC levels (P < 0.05). Conclusion: In a subset of the population in Qingdao, China, the ACAT1 rs10913733 polymorphism is not significantly associated with the risk of NAFLD. In all subjects and NAFLD patients, being a non-carrier of the T allele of ACAT1 rs10913733 is associated with higher blood cholesterol levels.
[1] | Rinella, M.E., Neuschwander-Tetri, B.A., Siddiqui, M.S., Abdelmalek, M.F., Caldwell, S., Barb, D., et al. (2023) AASLD Practice Guidance on the Clinical Assessment and Management of Nonalcoholic Fatty Liver Disease. Hepatology, 77, 1797-1835. https://doi.org/10.1097/hep.0000000000000323 |
[2] | 中华医学会肝病学分会. 代谢相关(非酒精性)脂肪性肝病防治指南(2024年版) [J]. 中华肝脏病杂志, 2024, 32(5): 418-434. |
[3] | Ekstedt, M., Nasr, P. and Kechagias, S. (2017) Natural History of NAFLD/NASH. Current Hepatology Reports, 16, 391-397. https://doi.org/10.1007/s11901-017-0378-2 |
[4] | Simon, T.G., Roelstraete, B., Khalili, H., Hagström, H. and Ludvigsson, J.F. (2020) Mortality in Biopsy-Confirmed Nonalcoholic Fatty Liver Disease: Results from a Nationwide Cohort. Gut, 70, 1375-1382. https://doi.org/10.1136/gutjnl-2020-322786 |
[5] | Lou, T., Yang, R. and Fan, J. (2024) The Global Burden of Fatty Liver Disease: The Major Impact of China. Hepatobiliary Surgery and Nutrition, 13, 119-123. https://doi.org/10.21037/hbsn-23-556 |
[6] | Li, H., Yu, X., Ou, X., Ouyang, X. and Tang, C. (2021) Hepatic Cholesterol Transport and Its Role in Non-Alcoholic Fatty Liver Disease and Atherosclerosis. Progress in Lipid Research, 83, Article ID: 101109. https://doi.org/10.1016/j.plipres.2021.101109 |
[7] | Melton, E.M., Li, H., Benson, J., Sohn, P., Huang, L., Song, B., et al. (2019) Myeloid Acat1/Soat1 KO Attenuates Pro-Inflammatory Responses in Macrophages and Protects against Atherosclerosis in a Model of Advanced Lesions. Journal of Biological Chemistry, 294, 15836-15849. https://doi.org/10.1074/jbc.ra119.010564 |
[8] | Wu, D., Yin, R., Aung, L.H.H., Li, Q., Yan, T., Zeng, X., et al. (2012) Sex-Specific Association of ACAT-1 Rs1044925 SNP and Serum Lipid Levels in the Hypercholesterolemic Subjects. Lipids in Health and Disease, 11, Article No. 9. https://doi.org/10.1186/1476-511x-11-9 |
[9] | Wang, Y., Wang, Y., Ma, Y., Fu, Z., Yang, Y., Ma, X., et al. (2017) acat-1 Gene Polymorphism Is Associated with Increased Susceptibility to Coronary Artery Disease in Chinese Han Population: A Case-Control Study. Oncotarget, 8, 89055-89063. https://doi.org/10.18632/oncotarget.21649 |
[10] | 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018更新版) [J]. 中华肝脏病杂志, 2018, 26(3): 195-203. |
[11] | Powell, E.E., Wong, V.W. and Rinella, M. (2021) Non-Alcoholic Fatty Liver Disease. The Lancet, 397, 2212-2224. https://doi.org/10.1016/s0140-6736(20)32511-3 |
[12] | Eslam, M., Sanyal, A.J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., et al. (2020) MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology, 158, 1999-2014.e1. https://doi.org/10.1053/j.gastro.2019.11.312 |
[13] | Zhang, X., Coker, O.O., Chu, E.S., Fu, K., Lau, H.C.H., Wang, Y., et al. (2020) Dietary Cholesterol Drives Fatty Liver-Associated Liver Cancer by Modulating Gut Microbiota and Metabolites. Gut, 70, 761-774. https://doi.org/10.1136/gutjnl-2019-319664 |
[14] | Liu, F., Tian, T., Zhang, Z., Xie, S., Yang, J., Zhu, L., et al. (2022) Long Non-Coding RNA SNHG6 Couples Cholesterol Sensing with mTORC1 Activation in Hepatocellular Carcinoma. Nature Metabolism, 4, 1022-1040. https://doi.org/10.1038/s42255-022-00616-7 |
[15] | Pham, H., Singaram, I., Sun, J., Ralko, A., Puckett, M., Sharma, A., et al. (2022) Development of a Novel Spatiotemporal Depletion System for Cellular Cholesterol. Journal of Lipid Research, 63, Article ID: 100178. https://doi.org/10.1016/j.jlr.2022.100178 |
[16] | Liu, J., Chang, C.C.Y., Westover, E.J., Covey, D.F. and Chang, T. (2005) Investigating the Allosterism of acyl-CoA: Cholesterol Acyltransferase (ACAT) by Using Various Sterols: In Vitro and Intact Cell Studies. Biochemical Journal, 391, 389-397. https://doi.org/10.1042/bj20050428 |
[17] | Tabas, I. (2002) Consequences of Cellular Cholesterol Accumulation: Basic Concepts and Physiological Implications. Journal of Clinical Investigation, 110, 905-911. https://doi.org/10.1172/jci0216452 |
[18] | Ioannou, G.N. (2016) The Role of Cholesterol in the Pathogenesis of Nash. Trends in Endocrinology & Metabolism, 27, 84-95. https://doi.org/10.1016/j.tem.2015.11.008 |
[19] | Puri, P., Baillie, R.A., Wiest, M.M., Mirshahi, F., Choudhury, J., Cheung, O., et al. (2007) A Lipidomic Analysis of Nonalcoholic Fatty Liver Disease. Hepatology, 46, 1081-1090. https://doi.org/10.1002/hep.21763 |
[20] | Klepper, C.M., Khurana, T., Sun, Q., Fei, L., Crimmins, N.A., Siegel, R., et al. (2023) BMI Metrics Are Poor Predictors of Pediatric Nonalcoholic Fatty Liver Disease Severity. Childhood Obesity, 19, 139-143. https://doi.org/10.1089/chi.2021.0316 |
[21] | 胡盛龙, 赵莉, 庄立琨, 刘守胜, 辛永宁, 宣世英. 血清细胞角蛋白-18水平与经磁共振成像质子密度脂肪分数量化的肝脏脂肪变性程度的相关性[J]. 实用医学杂志, 2022, 38(9): 1102-1107. |
[22] | 胡玉琼. 酯酰辅酶A: 胆固醇酰基转移酶1 (ACAT1)基因多态性与汉族人冠心病相关性研究[D]: [硕士学位论文]. 泸州: 西南医科大学内科学, 2015. |
[23] | Pipitone, R.M., Ciccioli, C., Infantino, G., La Mantia, C., Parisi, S., Tulone, A., et al. (2023) MAFLD: A Multisystem Disease. Therapeutic Advances in Endocrinology and Metabolism, 14, 1-23. https://doi.org/10.1177/20420188221145549 |
[24] | Yu, X., Fu, Y., Zhang, D., Yin, K. and Tang, C. (2013) Foam Cells in Atherosclerosis. Clinica Chimica Acta, 424, 245-252. https://doi.org/10.1016/j.cca.2013.06.006 |
[25] | Nissen, S.E., Tuzcu, E.M., Brewer, H.B., Sipahi, I., Nicholls, S.J., Ganz, P., et al. (2006) Effect of ACAT Inhibition on the Progression of Coronary Atherosclerosis. New England Journal of Medicine, 354, 1253-1263. https://doi.org/10.1056/nejmoa054699 |