Jiaxin Zhao, Huiying Zhou, Rui Wu, Chen Ruan, Cheng Wang, Jiawei Ding, Tao Zhang, Zheyu Fang, Huilin Zheng, Lei Zhang, Jie Zhou, Zhenhua Hu
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We explored the potential causal relationship between telomere length and liver fibrosis using Mendelian randomization (MR). Additionally, we used the expression quantitative trait loci (eQTL) method and GSE197112 data to identify genes related to liver fibrosis and senescence. Finally, the APOLD1 expression was validated using GSE89632.</p><p><strong>Results: </strong>Phenotypic age was associated with liver fibrosis occurrence in MASLD (OR = 1.08, 95 % CI 1.05-1.12). Subgroup analyses by BMI and age revealed differences. For obese or young to middle-aged MASLD patients, phenotypic age is significantly associated with liver fibrosis. (OR = 1.14, 95 % CI 1.10-1.18; OR = 1.07, 95 % CI 1.01-1.14 and OR = 1.14, 95 % CI 1.07-1.22). MR revealed a negative association between telomere length and liver fibrosis (IVW method: OR = 0.63288, 95 % CI 0.42498-0.94249). The gene APOLD1 was identified as a potential target through the intersection of the GEO dataset and eQTL genes.</p><p><strong>Conclusions: </strong>This study emphasized the link between biological aging and fibrosis in young to middle-aged obese MASLD patients. 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引用次数: 0
摘要
导言和目的:本研究旨在调查代谢功能障碍相关性脂肪性肝病(MASLD)患者的生物衰老与肝纤维化之间的关联:我们分析了 NHANES 2017-2020 年的数据,以计算表型年龄。使用受控衰减参数(CAP)、脂肪肝指数(FLI)和瞬态弹性成像(TE)确定肝脏脂肪变性和纤维化。采用多变量逻辑回归法计算了明显MASLD纤维化的几率(OR)和95%置信区间(CI),并进行了亚组分析。我们使用孟德尔随机法(MR)探讨了端粒长度与肝纤维化之间的潜在因果关系。此外,我们还使用表达定量性状位点(eQTL)方法和 GSE197112 数据来识别与肝纤维化和衰老相关的基因。最后,我们利用 GSE89632 验证了 APOLD1 的表达:结果:表型年龄与MASLD肝纤维化的发生相关(OR = 1.08,95% CI 1.05-1.12)。按体重指数和年龄进行的亚组分析显示出差异。对于肥胖或中青年 MASLD 患者,表型年龄与肝纤维化显著相关。(OR = 1.14,95% CI 1.10-1.18;OR = 1.07,95% CI 1.01-1.14;OR = 1.14,95% CI 1.07-1.22)。MR显示端粒长度与肝纤维化呈负相关(IVW法:OR = 0.63288,95% CI 0.42498-0.94249)。通过GEO数据集和eQTL基因的交叉,APOLD1基因被确定为潜在靶点:本研究强调了中青年肥胖 MASLD 患者的生物衰老与纤维化之间的联系。我们引入了表型年龄作为临床指标,并将 APOLD1 鉴定为潜在的治疗靶点。
Biological aging accelerates hepatic fibrosis: Insights from the NHANES 2017-2020 and genome-wide association study analysis.
Introduction and objectives: This study aimed to investigate the association between biological aging and liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).
Materials and methods: We analyzed NHANES 2017-2020 data to calculate phenotypic age. Hepatic steatosis and fibrosis were identified using controlled attenuation parameters (CAP), fatty liver index (FLI) and transient elastography (TE). The odds ratios (ORs) and 95 % confidence intervals (CI) for significant MASLD fibrosis were calculated using multivariate logistic regression, and subgroup analyses were performed. We explored the potential causal relationship between telomere length and liver fibrosis using Mendelian randomization (MR). Additionally, we used the expression quantitative trait loci (eQTL) method and GSE197112 data to identify genes related to liver fibrosis and senescence. Finally, the APOLD1 expression was validated using GSE89632.
Results: Phenotypic age was associated with liver fibrosis occurrence in MASLD (OR = 1.08, 95 % CI 1.05-1.12). Subgroup analyses by BMI and age revealed differences. For obese or young to middle-aged MASLD patients, phenotypic age is significantly associated with liver fibrosis. (OR = 1.14, 95 % CI 1.10-1.18; OR = 1.07, 95 % CI 1.01-1.14 and OR = 1.14, 95 % CI 1.07-1.22). MR revealed a negative association between telomere length and liver fibrosis (IVW method: OR = 0.63288, 95 % CI 0.42498-0.94249). The gene APOLD1 was identified as a potential target through the intersection of the GEO dataset and eQTL genes.
Conclusions: This study emphasized the link between biological aging and fibrosis in young to middle-aged obese MASLD patients. We introduced phenotypic age as a clinical indicator and identified APOLD1 as a potential therapeutic target.
期刊介绍:
Annals of Hepatology publishes original research on the biology and diseases of the liver in both humans and experimental models. Contributions may be submitted as regular articles. The journal also publishes concise reviews of both basic and clinical topics.