代谢相关脂肪性肝病患者中 PNPLA3 和 SIRT5 基因变异的相互作用与肝纤维化严重程度的关系。

Interaction Between PNPLA3 and SIRT5 Genetic Variants in Association with Liver Fibrosis Severity in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease.

机构信息

Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, Bangkok 10400, Thailand.

出版信息

Genes (Basel). 2024 Oct 24;15(11):1370. doi: 10.3390/genes15111370.

DOI:10.3390/genes15111370

PMID:39596570

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11593416/

Abstract

BACKGROUND/OBJECTIVES: This study evaluated the association between polymorphisms in the , , , and genes and the severity of fibrosis and steatosis in metabolic dysfunction-associated steatotic liver disease (MASLD).

METHODS

Fibrosis and steatosis were assessed by MRE and MRI-PDFF, respectively. The polymorphisms were determined by allelic discrimination in blood samples.

RESULTS

204 patients aged 57.0 ± 13.5 years were included. Sixty-two (30.4%) patients had significant fibrosis (≥F2). Among F2-F4 fibrosis, the rs738409 GG genotype was significantly higher than the CC + CG genotypes (44.9% vs. 21.4%, = 0.001). The rs12216101 GG vs. TT + TG genotypes also exhibited a similar trend (64.3% vs. 27.9%, = 0.012). In multivariate analysis, the GG genotype (OR = 3.48, 95%CI: 1.50-8.06; = 0.004) and rs12216101 GG genotype (OR = 5.43, 95%CI: 1.32-22.33; = 0.019) were independently associated with F2-F4 fibrosis. Additionally, the proportion of patients with F2-F4 fibrosis significantly increased with the number of combined risk genotypes. Among S2-S3 steatosis, the prevalence of AG + GG genotypes was higher than that of the AA genotype (37.5% vs. 23.9%, = 0.048) and independently associated with moderate/severe steatosis in multivariate analysis (OR = 2.26, 95%CI: 1.14-4.49; = 0.020).

CONCLUSIONS

Our data indicate that the and polymorphisms were independently and additively linked to significant fibrosis, while the polymorphism was associated with increased steatosis in Thai populations. These data might emphasize the importance of genetic variants in progressive MASLD.

摘要

背景/目的：本研究评估了、、、基因多态性与代谢相关脂肪性肝病（MASLD）中纤维化和脂肪变性严重程度之间的关联。

方法

通过 MRE 和 MRI-PDFF 分别评估纤维化和脂肪变性。通过血液样本中的等位基因鉴别确定多态性。

结果

纳入 204 例年龄 57.0±13.5 岁的患者。62 例（30.4%）患者存在显著纤维化（≥F2）。在 F2-F4 纤维化中，rs738409 GG 基因型明显高于 CC+CG 基因型（44.9%比 21.4%，=0.001）。rs12216101 GG 与 TT+TG 基因型也呈现出类似的趋势（64.3%比 27.9%，=0.012）。多变量分析中，GG 基因型（OR=3.48，95%CI：1.50-8.06；=0.004）和 rs12216101 GG 基因型（OR=5.43，95%CI：1.32-22.33；=0.019）与 F2-F4 纤维化独立相关。此外，随着联合风险基因型数量的增加，F2-F4 纤维化患者的比例显著增加。在 S2-S3 脂肪变性中，AG+GG 基因型的患病率高于 AA 基因型（37.5%比 23.9%，=0.048），且在多变量分析中与中重度脂肪变性独立相关（OR=2.26，95%CI：1.14-4.49；=0.020）。