Day C P
School of Clinical Medicine (Hepatology), Floor 4, William Leech Building, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Clin Liver Dis. 2004 Aug;8(3):673-91, xi. doi: 10.1016/j.cld.2004.04.001.
Although most people with obesity and type 2 diabetes will have steatosis, only a minority will ever develop nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Family studies suggest that genetic factors are important in disease progression, although dissecting genetic factors playing a role in NASH and fibrosis from those influencing the development established risk factors is difficult. Several approaches can be used to look for genetic factors playing a role in nonalcoholic fatty liver disease (NAFLD). In the future, genome-wide single nucleotide polymorphism (SNP) scanning of cases and controls may become feasible. To date, however,studies have relied on candidate gene, case control, allele association methodology. Recent, and as yet preliminary, studies have reported associations between steatosis severity, NASH, and fibrosis with genes whose products are involved in lipid metabolism,oxidative stress, and endotoxin-cytokine interactions. If confirmed,these associations will enhance understanding of disease pathogenesis,and accordingly, the ability to design effective therapies.
虽然大多数肥胖和2型糖尿病患者会有肝脂肪变性，但只有少数人会发展为非酒精性脂肪性肝炎（NASH）、肝纤维化和肝硬化。家族研究表明，遗传因素在疾病进展中很重要，尽管将在NASH和肝纤维化中起作用的遗传因素与那些影响已确定的危险因素发展的遗传因素区分开来很困难。有几种方法可用于寻找在非酒精性脂肪性肝病（NAFLD）中起作用的遗传因素。未来，对病例和对照进行全基因组单核苷酸多态性（SNP）扫描可能会变得可行。然而，迄今为止，研究一直依赖于候选基因、病例对照、等位基因关联方法。最近的、尚属初步的研究报告了肝脂肪变性严重程度、NASH和肝纤维化与某些基因之间的关联，这些基因的产物参与脂质代谢、氧化应激和内毒素-细胞因子相互作用。如果得到证实，这些关联将增进对疾病发病机制的理解，从而提高设计有效治疗方法的能力。
