ABCG1,即ATP结合盒转运蛋白G1,是一种重要的细胞膜转运蛋白,负责将细胞内的胆固醇转移到细胞外的HDL(高密度脂蛋白)颗粒中。ABCG1在维持细胞内胆固醇平衡、调节胆固醇的逆向转运和脂质代谢中发挥着关键作用。此外,ABCG1的活性还与动脉粥样硬化、糖尿病、肥胖等多种疾病的发生发展密切相关。
研究表明,ABCG1基因的DNA甲基化程度与血脂水平、糖尿病风险和抗精神病药物引起的代谢综合征等疾病相关。例如,Jiang等人发现,ABCG1基因DNA甲基化程度与辛伐他汀的降脂效果有关,甲基化程度越高,辛伐他汀的降脂效果越差[1]。Qie等人发现,ABCG1基因CpG13和CpG14位点的DNA甲基化程度与2型糖尿病风险增加相关,CpG15位点的甲基化程度变化也与糖尿病风险增加相关[2]。Zhou等人发现,抗精神病药物引起的代谢综合征患者中,ABCG1基因的DNA甲基化程度升高,且与总胆固醇和甘油三酯水平升高相关[3]。Wang等人发现,ABCG1基因启动子区域的多态性rs57137919与血浆HDL-C和LDL-C水平相关[4]。Chen等人发现,膳食中甲基供体营养素的摄入与ABCG1基因CpG19.20位点的DNA甲基化程度相关,且甲基化程度与中风风险相关[5]。
此外,ABCG1基因的表达和功能还受到多种因素的调控。例如,Shen等人发现,ABCG1基因敲除小鼠的转录组分析结果显示,与动脉粥样硬化相关的多种基因表达发生改变[6]。Rozhkova等人综述了ABCA1、ABCG1和SCARB1基因表达在动脉粥样硬化中的调节机制,包括基因多态性、转录因子、长链非编码RNA和微小RNA等[7]。Miroshnikova等人发现,RORa转录因子在调节ABCA1和ABCG1基因在腹内脂肪组织中的表达中发挥重要作用[8]。
综上所述,ABCG1基因在胆固醇代谢、脂质稳态和多种疾病的发生发展中发挥着重要作用。DNA甲基化程度、基因多态性、转录因子和表观遗传调控等因素共同影响着ABCG1基因的表达和功能。深入研究ABCG1基因的调控机制及其与疾病的关系,有助于揭示疾病的发生发展机制,为疾病的预防、诊断和治疗提供新的思路和策略。
参考文献:
1. Jiang, Shanqun, Cai, Qianru, Zhang, Di, Hu, Shengnan, Venners, Scott A. 2020. Effect of ABCG1 gene DNA methylations on the lipid-lowering efficacy of simvastatin. In Pharmacogenomics, 22, 27-39. doi:10.2217/pgs-2020-0068. https://pubmed.ncbi.nlm.nih.gov/33356546/
2. Qie, Ranran, Chen, Qing, Wang, Tieqiang, Hu, Dongsheng, Zhang, Ming. 2020. Association of ABCG1 gene methylation and its dynamic change status with incident type 2 diabetes mellitus: the Rural Chinese Cohort Study. In Journal of human genetics, 66, 347-357. doi:10.1038/s10038-020-00848-z. https://pubmed.ncbi.nlm.nih.gov/32968204/
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