|
|
ACAT1 rs11545566多态性与非酒精性脂肪性肝病易感性的相关性
|
Abstract:
目的：探究中国青岛地区乙酰辅酶A乙酰转移酶1 (acetyl-CoA acetyltransferase 1, ACAT1)基因rs11545566位点多态性与非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)易感性的相关性。方法：纳入于青岛市市立医院收集的NAFLD患者226例，健康对照141例。收集所有受试者血液标本，提取DNA，通过聚合酶链反应的方法扩增DNA，并检测ACAT1基因rs11545566位点的基因型。收集并分析患者的临床资料及实验室指标。符合正态分布的计量资料采用t检验，不符合正态分布的计量资料采用Wilcoxon秩和检验进行组间比较，使用χ2检验分析NAFLD和对照组的基因型及等位基因分布差异。结果：ACAT1 rs11545566位点在NAFLD组和对照组的基因型与等位基因分布差异均无统计学意义(P > 0.05)。ACAT1 rs11545566位点G等位基因携带者比非携带者ALT水平更低(P = 0.038)。结论：在中国青岛汉族人群中，ACAT1 rs11545566位点多态性与NAFLD易感性无显著相关性。ACAT1 rs11545566 位点G等位基因携带可能与低ALT水平有关。
Objective: To explore the polymorphism of acetyl-CoA acetyltransferase 1 (ACAT1) rs11545566 locus and non-alcoholic fatty liver disease in Qingdao region of China association with susceptibility to NAFLD. Methods: 226 patients with NAFLD and 141 healthy controls admitted to Qingdao Municipal Hospital were included. Blood samples were collected from all subjects and DNA was extracted. Then DNA was amplified by polymerase chain reaction and we genotyped the rs11545566 locus of the ACAT1 gene. Clinical data and laboratory indicators were collected and analyzed. T-test was used for measurement data conforming to normal distribution, and Wilcoxon rank sum test was used for comparison between groups for measurement data not conforming to normal distribution. χ2 test was used to analyze the differences in genotype and allele distribution between NAFLD and control group. Results: There were no significant differences in genotype and allele distribution of ACAT1 rs11545566 between NAFLD group and control group (P > 0.05). ACAT1 rs11545566 G allele carriers have lower ALT levels than non-carriers (P = 0.038). Conclusion: There is no significant correlation between ACAT1 rs11545566 polymorphism and NAFLD in Qingdao Han population. ACAT1 rs11545566 G allele is associated with lower levels of ALT.
| [1] | Younossi, Z.M., Koenig, A.B., Abdelatif, D., Fazel, Y., Henry, L. and Wymer, M. (2016) Global Epidemiology of Nonalcoholic Fatty Liver Disease—Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes. Hepatology, 64, 73-84. https://doi.org/10.1002/hep.28431 |
| [2] | 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]. 传染病信息, 2018, 31(5): 393-402+420. |
| [3] | Diehl, A.M., Goodman, Z. and Ishak, K.G. (1988) Alcohollike Liver Disease in Nonalcoholics. Gastroenterology, 95, 1056-1062. https://doi.org/10.1016/0016-5085(88)90183-7 |
| [4] | Ludwig, J., Viggiano, T.R., McGill, D.B. and Ott, B.J. (1980) Nonalcoholic Steatohepatitis Mayo Clinic Experiences with a Hitherto Unnamed Disease. Mayo Clinic Proceedings, 55, 434-438. https://doi.org/10.1016/s0025-6196(24)00530-5 |
| [5] | Zhou, Z., Sang, L., Wang, J., Song, L., Zhu, L., Wang, Y., et al. (2021) Relationships among N, n-Dimethylformamide Exposure, CYP2E1 and TM6SF2 Genes, and Non-Alcoholic Fatty Liver Disease. Ecotoxicology and Environmental Safety, 228, Article 112986. https://doi.org/10.1016/j.ecoenv.2021.112986 |
| [6] | Romeo, S., Kozlitina, J., Xing, C., Pertsemlidis, A., Cox, D., Pennacchio, L.A., et al. (2008) Genetic Variation in PNPLA3 Confers Susceptibility to Nonalcoholic Fatty Liver Disease. Nature Genetics, 40, 1461-1465. https://doi.org/10.1038/ng.257 |
| [7] | Yoneda, M., Hotta, K., Nozaki, Y., Endo, H., Uchiyama, T., Mawatari, H., et al. (2008) Association between PPARGC1A Polymorphisms and the Occurrence of Nonalcoholic Fatty Liver Disease (NAFLD). BMC Gastroenterology, 8, Article No. 27. https://doi.org/10.1186/1471-230x-8-27 |
| [8] | Taghvaei, S., Saremi, L. and Babaniamansour, S. (2021) Computational Analysis of Gly482ser Single-Nucleotide Polymorphism in PPARGC1A Gene Associated with CAD, NAFLD, T2DM, Obesity, Hypertension, and Metabolic Diseases. PPAR Research, 2021, 1-12. https://doi.org/10.1155/2021/5544233 |
| [9] | Song, J., Da Costa, K.A., Fischer, L.M., Kohlmeier, M., Kwock, L., Wang, S., et al. (2005) Polymorphism of Thepemtgene and Susceptibility to Nonalcoholic Fatty Liver Disease (NAFLD). The FASEB Journal, 19, 1266-1271. https://doi.org/10.1096/fj.04-3580com |
| [10] | Wei, Z., Li-Qun, Z., Xiao-Ling, H., Jian, Q. and Guo-Yue, Y. (2016) Association of Adiponectin Gene Polymorphisms and Additional Gene-Gene Interaction with Nonalcoholic Fatty Liver Disease in the Chinese Han Population. Hepatology International, 10, 511-517. https://doi.org/10.1007/s12072-015-9687-0 |
| [11] | Dove, D.E., Su, Y.R., Zhang, W., Jerome, W.G., Swift, L.L., Linton, M.F., et al. (2005) ACAT1 Deficiency Disrupts Cholesterol Efflux and Alters Cellular Morphology in Macrophages. Arteriosclerosis, Thrombosis, and Vascular Biology, 25, 128-134. https://doi.org/10.1161/01.atv.0000148323.94021.e5 |
| [12] | Wang, Y., Wang, Y., Ma, Y., Fu, Z., Yang, Y., Ma, X., et al. (2017) ACAT-1Gene 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 |
| [13] | Abosheaishaa, H., Hussein, M., Ghallab, M., Abdelhamid, M., Balassiano, N., Ahammed, M.R., et al. (2024) Association between Non-Alcoholic Fatty Liver Disease and Coronary Artery Disease Outcomes: A Systematic Review and Meta-Analysis. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 18, Article 102938. https://doi.org/10.1016/j.dsx.2023.102938 |
| [14] | Chitturi, S., Wong, V.W., Chan, W., Wong, G.L., Wong, S.K., Sollano, J., et al. (2017) The Asia-Pacific Working Party on Non-Alcoholic Fatty Liver Disease Guidelines 2017—Part 2: Management and Special Groups. Journal of Gastroenterology and Hepatology, 33, 86-98. https://doi.org/10.1111/jgh.13856 |
| [15] | Dove, D.E., Su, Y.R., Swift, L.L., Linton, M.F. and Fazio, S. (2006) ACAT1 Deficiency Increases Cholesterol Synthesis in Mouse Peritoneal Macrophages. Atherosclerosis, 186, 267-274. https://doi.org/10.1016/j.atherosclerosis.2005.08.005 |
| [16] | Peng, K., Wang, S., Liu, R., Zhou, L., Jeong, G.H., Jeong, I.H., et al. (2023) Effects of UBE3A on Cell and Liver Metabolism through the Ubiquitination of PDHA1 and ACAT1. Biochemistry, 62, 1274-1286. https://doi.org/10.1021/acs.biochem.2c00624 |
| [17] | Chang, T., Chang, C.C.Y., Lin, S., Yu, C., Li, B. and Miyazaki, A. (2001) Roles of Acyl-Coenzyme A: Cholesterol Acyltransferase-1 and-2. Current Opinion in Lipidology, 12, 289-296. https://doi.org/10.1097/00041433-200106000-00008 |
| [18] | Yin, R., Wu, D., Aung, L.H.H., Yan, T., Cao, X., Long, X., et al. (2012) Several Lipid-Related Gene Polymorphisms Interact with Overweight/Obesity to Modulate Blood Pressure Levels. International Journal of Molecular Sciences, 13, 12062-12081. https://doi.org/10.3390/ijms130912062 |
| [19] | Wu, D., Yin, R., Cao, X. and Chen, W. (2014) Association between Single Nucleotide Polymorphism Rs1044925 and the Risk of Coronary Artery Disease and Ischemic Stroke. International Journal of Molecular Sciences, 15, 3546-3559. https://doi.org/10.3390/ijms15033546 |
| [20] | Rashkovan, M., Albero, R., Gianni, F., Perez-Duran, P., Miller, H.I., Mackey, A.L., et al. (2022) Intracellular Cholesterol Pools Regulate Oncogenic Signaling and Epigenetic Circuitries in Early T-Cell Precursor Acute Lymphoblastic Leukemia. Cancer Discovery, 12, 856-871. https://doi.org/10.1158/2159-8290.cd-21-0551 |
| [21] | Wang, M., Wang, W., You, S., Hou, Z., Ji, M., Xue, N., et al. (2023) ACAT1 Deficiency in Myeloid Cells Promotes Glioblastoma Progression by Enhancing the Accumulation of Myeloid-Derived Suppressor Cells. Acta Pharmaceutica Sinica B, 13, 4733-4747. https://doi.org/10.1016/j.apsb.2023.09.005 |
| [22] | Zhang, G., Huang, R., Zhao, H., Xia, Y., Huang, H., Qian, M., et al. (2023) ACAT1-Mediated METTL3 Acetylation Inhibits Cell Migration and Invasion in Triple Negative Breast Cancer. Genes & Immunity, 24, 99-107. https://doi.org/10.1038/s41435-023-00202-1 |
| [23] | Chen, L., Peng, T., Luo, Y., Zhou, F., Wang, G., Qian, K., et al. (2019) ACAT1 and Metabolism-Related Pathways Are Essential for the Progression of Clear Cell Renal Cell Carcinoma (CCRCC), as Determined by Co-Expression Network Analysis. Frontiers in Oncology, 9, Article 957. https://doi.org/10.3389/fonc.2019.00957 |
| [24] | Wang, T., Wang, G., Shan, D., Fang, Y., Zhou, F., Yu, M., et al. (2024) ACAT1 Promotes Proliferation and Metastasis of Bladder Cancer via Akt/GSK3β/c-Myc Signaling Pathway. Journal of Cancer, 15, 3297-3312. https://doi.org/10.7150/jca.95549 |
| [25] | Bryleva, E.Y., Rogers, M.A., Chang, C.C.Y., Buen, F., Harris, B.T., Rousselet, E., et al. (2010) ACAT1 Gene Ablation Increases 24(s)-Hydroxycholesterol Content in the Brain and Ameliorates Amyloid Pathology in Mice with AD. Proceedings of the National Academy of Sciences, 107, 3081-3086. https://doi.org/10.1073/pnas.0913828107 |
| [26] | Mao, T., Qin, F., Zhang, M., Li, J., Li, J. and Lai, M. (2023) Elevated Serum Β-Hydroxybutyrate, a Circulating Ketone Metabolite, Accelerates Colorectal Cancer Proliferation and Metastasis via ACAT1. Oncogene, 42, 1889-1899. https://doi.org/10.1038/s41388-023-02700-y |
| [27] | Yang, W., Bai, Y., Xiong, Y., Zhang, J., Chen, S., Zheng, X., et al. (2016) Potentiating the Antitumour Response of CD8+ T Cells by Modulating Cholesterol Metabolism. Nature, 531, 651-655. https://doi.org/10.1038/nature17412 |
| [28] | Wang, Q., Du, T., Zhang, Z., Zhang, Q., Zhang, J., Li, W., et al. (2024) Target Fishing and Mechanistic Insights of the Natural Anticancer Drug Candidate Chlorogenic Acid. Acta Pharmaceutica Sinica B, 14, 4431-4442. https://doi.org/10.1016/j.apsb.2024.07.005 |
