Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia.
Medical School, Sir Charles Gairdner Hospital Unit, University of Western Australia, Nedlands, WA, Australia.
PLoS One. 2020 Dec 11;15(12):e0243590. doi: 10.1371/journal.pone.0243590. eCollection 2020.
Metabolic associated fatty liver disease (MAFLD) is the most prevalent liver disease in Western nations, with high heritability. A recent study of Japanese patients with the disease suggested that TLL1 rs17047200 is associated with fibrosis; whether a similar association is observed in Caucasian patients with MAFLD is unknown. We investigated the association of the TLL1 rs17047200 polymorphism with liver fibrosis in a cohort of Caucasian patients with MAFLD (n = 728). We also investigated whether TLL1 expression is altered during liver injury in humans, in murine models of fibrosis, and in in-vitro. While TLL1 expression is upregulated in the liver of humans with MAFLD and in mice, the rs17047200 variant was not associated with fibrosis or any other histological features, or with hepatic TLL1 expression. In conclusion, the TLL1 rs17047200 variant is not a risk variant for fibrosis in Caucasian patients with MAFLD. However, TLL1 could be involved in the pathogenesis of liver fibrosis.
代谢相关性脂肪性肝病（MAFLD）是西方国家最常见的肝脏疾病，具有较高的遗传性。最近一项针对日本 MAFLD 患者的研究表明，TLL1 rs17047200 与纤维化有关；但在 MAFLD 的白种人群中是否存在类似的关联尚不清楚。我们研究了 TLL1 rs17047200 多态性与 MAFLD 白种人群肝纤维化的相关性（n = 728）。我们还研究了 TLL1 表达在人类肝损伤、纤维化的鼠模型以及体外是否发生改变。虽然 MAFLD 患者和小鼠的肝脏中 TLL1 表达上调，但 rs17047200 变异与纤维化或任何其他组织学特征或肝 TLL1 表达无关。总之，TLL1 rs17047200 变异不是白种人 MAFLD 患者纤维化的风险变异。然而，TLL1 可能参与了肝纤维化的发病机制。
