Saki Sara, Saki Nader, Poustchi Hossein, Malekzadeh Reza
Tehran University of Medical Sciences, Tehran, Iran.
Hoveizeh Cohort Study, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Middle East J Dig Dis. 2020 Apr;12(2):65-88. doi: 10.34172/mejdd.2020.166.
Recent evidence has demonstrated a strong interplay and multifaceted relationship between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). CVD is the major cause of death in patients with NAFLD. NAFLD also has strong associations with diabetes and metabolic syndrome. In this comprehensive review, we aimed to overview the primary environmental and genetic risk factors of NAFLD, and CVD and also focus on the genetic aspects of these two disorders. NAFLD and CVD are both heterogeneous diseases with common genetic and molecular pathways. We have searched for the latest published articles regarding this matter and tried to provide an overview of recent insights into the genetic aspects of NAFLD and CVD. The common genetic and molecular pathways involved in NAFLD and CVD are insulin resistance (IR), subclinical inflammation, oxidative stress, and atherogenic dyslipidemia. According to an investigation, the exact associations between genomic characteristics of NAFLD and CVD and casual relationships are not fully determined. Different gene polymorphisms have been identified as the genetic components of the NAFLDCVD association. Some of the most documented ones of these gene polymorphisms are patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), adiponectin-encoding gene (ADIPOQ), apolipoprotein C3 (APOC3), peroxisome proliferator-activated receptors (PPAR), leptin receptor (LEPR), sterol regulatory element-binding proteins (SREBP), tumor necrosis factor-alpha (TNF-α), microsomal triglyceride transfer protein (MTTP), manganese superoxide dismutase (MnSOD), membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), and mutation in DYRK1B that substitutes cysteine for arginine at position 102 in kinase-like domain. Further cohort studies with a significant sample size using advanced genomic assessments and next-generation sequencing techniques are needed to shed more light on genetic associations between NAFLD and CVD.
近期证据表明，非酒精性脂肪性肝病（NAFLD）与心血管疾病（CVD）之间存在着强烈的相互作用和多方面的关系。CVD是NAFLD患者的主要死因。NAFLD还与糖尿病和代谢综合征密切相关。在这篇综述中，我们旨在概述NAFLD和CVD的主要环境和遗传危险因素，并着重关注这两种疾病的遗传方面。NAFLD和CVD都是具有共同遗传和分子途径的异质性疾病。我们检索了有关此事的最新发表文章，并试图概述对NAFLD和CVD遗传方面的最新见解。NAFLD和CVD中涉及的共同遗传和分子途径包括胰岛素抵抗（IR）、亚临床炎症、氧化应激和致动脉粥样硬化血脂异常。根据一项调查，NAFLD和CVD的基因组特征与因果关系的确切关联尚未完全确定。不同的基因多态性已被确定为NAFLD与CVD关联的遗传成分。这些基因多态性中记录最多的一些包括含patatin样磷脂酶结构域蛋白3（PNPLA3）、跨膜6超家族成员2（TM6SF2）、羟基类固醇17-β脱氢酶13（HSD17B13）、脂联素编码基因（ADIPOQ）、载脂蛋白C3（APOC3）、过氧化物酶体增殖物激活受体（PPAR）、瘦素受体（LEPR）、固醇调节元件结合蛋白（SREBP）、肿瘤坏死因子-α（TNF-α）、微粒体甘油三酯转移蛋白（MTTP）、锰超氧化物歧化酶（MnSOD）、含膜结合O-酰基转移酶结构域7（MBOAT7）以及DYRK1B中激酶样结构域第102位的精氨酸被半胱氨酸替代的突变。需要使用先进的基因组评估和下一代测序技术进行更多有显著样本量的队列研究，以进一步阐明NAFLD和CVD之间的遗传关联。
