Aravinthan Aloysious, Mells George, Allison Michael, Leathart Julian, Kotronen Anna, Yki-Jarvinen Hannele, Daly Ann K, Day Christopher P, Anstee Quentin M, Alexander Graeme
Department of Medicine; University of Cambridge; Cambridge, UK.
Institute of Cellular Medicine; Newcastle University; Newcastle upon Tyne, UK.
Cell Cycle. 2014;13(9):1489-94. doi: 10.4161/cc.28471. Epub 2014 Mar 11.
Non-alcohol-related fatty liver disease (NAFLD) encompasses a wide spectrum, ranging from steatosis alone to steatohepatitis and fibrosis. Presence of steatohepatitis and fibrosis are key hallmarks of disease progression. Previous studies have demonstrated an association between hepatocyte p21 expression and fibrosis stage in NAFLD. The aim of this study is to investigate the association between the variants of CDKN1A, which encodes p21, and disease progression in NAFLD. To this end, the relation between CDKN1A polymorphism and liver fibrosis was studied in 2 cohorts of biopsy-proven NAFLD patients from UK (n = 323) and Finland (n = 123). Genotyping was performed using DNA isolated from lymphocytes collected at the time of liver biopsy. The findings of the UK cohort were tested in the Finnish cohort. Both the UK and Finnish cohorts were significantly different from each other in basic demographics. In the UK cohort, rs762623, of the 6 SNPs across CDKN1A tested, was significantly associated with disease progression in NAFLD. This association was confirmed in the Finnish cohort. Despite the influence on fibrosis development, SNPs across CDKN1A did not affect the progression of liver fibrosis. In conclusion, CDKN1A variant rs762623 is associated with the development but not the propagation of progressive liver disease in NAFLD.
非酒精性脂肪性肝病（NAFLD）涵盖范围广泛，从单纯性脂肪变性到脂肪性肝炎和纤维化。脂肪性肝炎和纤维化的存在是疾病进展的关键标志。先前的研究表明，NAFLD中肝细胞p21表达与纤维化阶段之间存在关联。本研究的目的是调查编码p21的CDKN1A变体与NAFLD疾病进展之间的关联。为此，在来自英国（n = 323）和芬兰（n = 123）的2组经活检证实的NAFLD患者队列中研究了CDKN1A多态性与肝纤维化之间的关系。使用从肝活检时收集的淋巴细胞中分离的DNA进行基因分型。英国队列的研究结果在芬兰队列中进行了验证。英国和芬兰队列在基本人口统计学方面彼此存在显著差异。在英国队列中，所检测的CDKN1A的6个单核苷酸多态性（SNP）中的rs762623与NAFLD的疾病进展显著相关。这一关联在芬兰队列中得到了证实。尽管对纤维化发展有影响，但CDKN1A的SNP并未影响肝纤维化的进展。总之，CDKN1A变体rs762623与NAFLD中进行性肝病的发展有关，但与传播无关。
