TLR4多态性与NAFLD易感性的相关性
Association between TLR4 Polymorphism and NAFLD Susceptibility
DOI: 10.12677/ACM.2023.1371508, PDF,   
作者: 赵守林, 宣世英*:青岛大学附属青岛市市立医院感染性疾病科,山东 青岛;赵真真:青岛大学附属青岛市市立医院临床研究中心,山东 青岛
关键词: 非酒精性脂肪性肝病Toll样受体4单核苷酸多态性Nonalcoholic Fatty Liver Disease Toll-Like Receptor 4 Single Nucleotide Polymorphism
摘要: 目的:探究中国青岛地区人群Toll样受体4 (Toll-like receptors 4, TLR4) rs1927914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2020年12月~2022年06月青岛市市立医院收入院的NAFLD患者218例,健康对照者101例。提取受试者血液中的DNA,使用多聚酶链反应(polymerase chain reaction, PCR)的方法扩增DNA,并检测TLR4基因rs1927914位点的基因型。收集并分析患者的与脂质代谢及肝脏代谢状态相关的指标。使用χ2检验分析基因型及等位基因频率。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。结果:NAFLD组和对照组TLR4 rs1927914位点的基因型与等位基因分布差异均无统计学意义。结论:在青岛地区人群中,TLR4 rs1927914位点多态性与NAFLD的无明显相关性。
Abstract: Objective: To explore the polymorphism of Toll-like receptors 4 (TLR4) rs1927914 locus and non- alcoholic fatty liver disease in Qingdao population of China association with susceptibility to NAFLD. Methods: 218 patients with NAFLD and 101 healthy controls admitted to Qingdao Municipal Hospi-tal from December 2020 to June 2022 were included. DNA was extracted from the subjects’ blood, amplified using polymerase chain reaction (PCR), and genotypes at rs1927914 locus of the TLR4 gene were detected. Indicators related to lipid metabolism and liver metabolic status were collect-ed and analyzed. Genotype and allele frequency were analyzed using χ2 test. 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. Results: There were no significant differences in genotype and allele distribution of TLR4 rs1927914 be-tween NAFLD group and control group. Conclusion: There is no significant correlation between TLR4 rs1927914 polymorphism and NAFLD in Qingdao population.
文章引用:赵守林, 赵真真, 宣世英. TLR4多态性与NAFLD易感性的相关性[J]. 临床医学进展, 2023, 13(7): 10796-10802. https://doi.org/10.12677/ACM.2023.1371508

参考文献

[1] Paik, J.M., Golabi, P., Younossi, Y., Mishra, A. and Younossi, Z.M. (2020) Changes in the Global Burden of Chronic Liver Diseases from 2012 to 2017: The Growing Impact of NAFLD. Hepatology, 72, 1605-1616. [Google Scholar] [CrossRef] [PubMed]
[2] Powell, E.E., Wong, V.W.S. and Rinella, M. (2021) Non-Alcoholic Fatty Liver Disease. The Lancet, 397, 2212-2224. [Google Scholar] [CrossRef
[3] Estes, C., Anstee, Q.M., Arias-Loste, M.T., et al. (2018) Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom and United States for the Period 2016-2030. Journal of Hepatology, 69, 896-904. [Google Scholar] [CrossRef] [PubMed]
[4] Bianco, C., Jamialahmadi, O., Pelusi, S., et al. (2021) Non-Invasive Stratification of Hepatocellular Carcinoma Risk in Non-Alcoholic Fatty Liver Using Polygenic Risk Scores. Journal of Hepatology, 74, 775-782. [Google Scholar] [CrossRef] [PubMed]
[5] Luukkonen, P.K., Qadri, S., Ahlholm, N., et al. (2021) Distinct Contributions of Metabolic Dysfunction and Genetic Risk Factors in the Pathogenesis of Non-Alcoholic Fatty Liver Disease. The Journal of Hepatology, 76, 526-535.
[6] De Vincentis, A., Tavaglione, F., Jamialahmadi, O., et al. (2022) A Polygenic Risk Score to Refine Risk Stratification and Prediction for Severe Liver Disease by Clinical Fibrosis Scores. Clinical Gastroenterology and Hepatology, 20, 658-673. [Google Scholar] [CrossRef] [PubMed]
[7] Trepo, E. and Valenti, L. (2020) Update on NAFLD Genetics: From New Variants to the Clinic. Journal of Hepatology, 72, 1196-1209. [Google Scholar] [CrossRef] [PubMed]
[8] Ciesielska, A., Matyjek, M. and Kwiatkowska, K. (2021) TLR4 and CD14 Trafficking and Its Influence on LPS-Induced Pro-Inflammatory Signaling. Cellular and Molec-ular Life Sciences, 78, 1233-1261. [Google Scholar] [CrossRef] [PubMed]
[9] Plociennikowska, A., Hromada-Judycka, A., Borzecka, K. and Kwiatkowska, K. (2015) Co-Operation of TLR4 and Raft Proteins in LPS-Induced Pro-Inflammatory Signaling. Cellular and Molecular Life Sciences, 72, 557-581. [Google Scholar] [CrossRef] [PubMed]
[10] Gao, H.H., Li, W., Shou, X.Y. and Mao, J.-H. (2023) Correlation between Toll-Like Receptor Gene Polymorphisms and Idiopathic Nephrotic Syndrome in Chinese Children. Current Medical Science, 43, 585-591. [Google Scholar] [CrossRef] [PubMed]
[11] Li, T., Jing, J.J., Dong, N.N., Liu, X. and Ma, C. (2021) TLR4 rs1927914 Polymorphism Contributes to Serum TLR4 Levels in Patients with Aortic Aneurysm. Experimental and Mo-lecular Pathology, 119, Article ID: 104609. [Google Scholar] [CrossRef] [PubMed]
[12] Xu, Y.X., Jiang, Z.X., Huang, J.H., Meng, Q., Coh, P. and Tao, L. (2015) The Association between Toll-Like Receptor 4 Polymorphisms and Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes. British Journal of Ophthalmology, 99, 1301-1305. [Google Scholar] [CrossRef] [PubMed]
[13] Drozdz, K., Nabrdalik, K., Hajzler, W., et al. (2022) Met-abolic-Associated Fatty Liver Disease (MAFLD), Diabetes, and Cardiovascular Disease: Associations with Fructose Metabolism and Gut Microbiota. Nutrients, 14, Article 103. [Google Scholar] [CrossRef] [PubMed]
[14] Cohen, J.C., Horton, J.D. and Hobbs, H.H. (2011) Human Fatty Liver Disease: Old Questions and New Insights. Science, 332, 1519-1523. [Google Scholar] [CrossRef] [PubMed]
[15] Heeren, J. and Scheja, L. (2021) Metabolic-Associated Fatty Liver Disease and Lipoprotein Metabolism. Molecular Metabolism, 50, Article ID: 101238. [Google Scholar] [CrossRef] [PubMed]
[16] Buzzetti, E., Pinzani, M. and Tsochatzis, E.A. (2016) The Mul-tiple-Hit Pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD). Metabolism-Clinical and Experimental, 65, 1038-1048. [Google Scholar] [CrossRef] [PubMed]
[17] Li, T., Jing, J.J., Sun, L.P., et al. (2019) TLR4 and MMP2 Polymorphisms and Their Associations with Cardiovascular Risk Factors in Susceptibility to Aortic Aneurysmal Dis-eases. Bioscience Reports, 39, BSR20181591.. [Google Scholar] [CrossRef
[18] Singh, K., Singh, V.K., Agrawal, N.K., Gupta, S.K. and Singh, K. (2013) Association of Toll-Like Receptor 4 Polymorphisms with Diabetic Foot Ulcers and Application of Artificial Neu-ral Network in DFU Risk Assessment in Type 2 Diabetes Patients. BioMed Research International, 2013, Article ID: 318686. [Google Scholar] [CrossRef] [PubMed]
[19] Zhang, H.M., Gao, H., Li, A., et al. (2022) TLR4 Regulatory Region Variants Reduce the Susceptibility of Small-Cell Lung Cancer in Chinese Population. European Journal of Can-cer Prevention, 31, 363-368. [Google Scholar] [CrossRef
[20] Li, J.Y., Wu, H.J., Gao, H., et al. (2021) TLR4 Promoter rs1927914 Variant Contributes to the Susceptibility of Esophageal Squamous Cell Carcinoma in the Chinese Population. PeerJ, 9, e10754. [Google Scholar] [CrossRef] [PubMed]
[21] Shi, G., Wang, T.T., Li, S.J., et al. (2016) TLR2 and TLR4 Polymorphisms in Southern Chinese Psoriasis Vulgaris patients. Journal of Dermatological Science, 83, 145-147. [Google Scholar] [CrossRef] [PubMed]
[22] Gu, L., Huang, J.Y., Liang, B.Y., et al. (2018) TLR4 Poly-morphisms Affect Stroke Risk and Inflammatory Response in Chinese Ischemic Stroke Patients. Neurological Sciences, 39, 127-133. [Google Scholar] [CrossRef] [PubMed]
[23] Chen, R.X., Dai, M.D., Zhang, Q.Z., Lu, M.P., Wang, M.L., Yin, M., Zhu, X.J., Wu, Z.F., Zhang, Z.D. and Cheng, L. (2022) TLR Signaling Pathway Gene Polymor-phisms, Gene-Gene and Gene-Environment Interactions in Allergic Rhinitis. Journal of Inflammation Research, 15, 3613-3630. [Google Scholar] [CrossRef
[24] Maciel-Fiuza, M.F., Costa, P.D.S., Kowalski, T.W., et al. (2022) Evaluation of Polymorphisms in Toll-Like Receptor Genes as Biomarkers of the Response to Treatment of Ery-thema Nodosum Leprosum. Frontiers in Medicine, 8, Article 713143. [Google Scholar] [CrossRef] [PubMed]
[25] Younossi, Z.M., Koenig, A.B., Abdelatif, D., et al. (2016) Global Epidemiology of Nonalcoholic Fatty Liver Disease- Meta-Analytic Assessment of Prevalence, Incidence and Outcomes. Hepatology, 64, 73-84. [Google Scholar] [CrossRef] [PubMed]
[26] Zhao, X.F., An, X.D., Yang, C.Q., et al. (2023) The Crucial Role and Mechanism of Insulin Resistance in Metabolic Disease. Frontiers in Endocrinology, 14, Article 1143239. [Google Scholar] [CrossRef] [PubMed]
[27] Shi, G.J., Wang, C.X., Zhang, P., Ji, L., Xu, S., Tan, X. and Li, H. (2017) Donor Polymorphisms of Toll-like Receptor 4 rs1927914 Associated with the Risk of Hepatocellular Carci-noma Recurrence Following Liver Transplantation. Archives of Medical Research, 48, 553-560. [Google Scholar] [CrossRef] [PubMed]
[28] Shi, M.M., Xu, X.Q., Chen, H., et al. (2011) Single Nucleotide Polymorphisms of Toll-Like Receptor 4 Decrease the Risk of Development of Hepatocellular Carcinoma. PLOS ONE, 6, e19466. [Google Scholar] [CrossRef] [PubMed]
[29] Marchesini, G., Bugianesi, E., Forlani, G., et al. (2003) Nonal-coholic Fatty Liver, Steatohepatitis and the Metabolic Syndrome. Hepatology, 37, 917-923. [Google Scholar] [CrossRef] [PubMed]
[30] Newberry. E.P., Hall, Z., Xie, Y., et al. (2021) Liver-Specific Dele-tion of Mouse Tm6sf2 Promotes Steatosis, Fibrosis, and Hepatocellular Cancer. Hepatology, 74, 1203-1219. [Google Scholar] [CrossRef] [PubMed]
[31] Kozlitina, J., Smagris, E., Stender, S., et al. (2014) Exome-Wide Associa-tion Study Identifies a TM6SF2 Variant that Confers Susceptibility to Nonalcoholic Fatty Liver Disease. Nature Genetics, 46, 352-356. [Google Scholar] [CrossRef] [PubMed]
[32] Loomba, R., Friedman, S.L. and Shulman, G.I. (2021) Mechanisms and Dis-ease Consequences of Nonalcoholic Fatty Liver Disease. Cell, 184, 2537-2564. [Google Scholar] [CrossRef] [PubMed]
[33] Du, D.Y., Liu, C., Qin, M.Y., Zhang,X., Xi, T., Yuan, S., Hao, H. And Xiong, J. (2022) Metabolic Dysregulation and Emerging Therapeutical Targets for Hepatocellular Carcinoma. Acta Pharmaceutica Sinica B, 12, 558-580. [Google Scholar] [CrossRef] [PubMed]
[34] Mcglynn, K.A., Petrick, J.L. and El-Serag, H.B. (2021) Epidemi-ology of Hepatocellular Carcinoma. Hepatology, 73, 4-13. [Google Scholar] [CrossRef] [PubMed]