Division of Gastroenterology, NAFLD Research Center, University of California at San Diego, La Jolla, CA, USA.
Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
Aliment Pharmacol Ther. 2021 Jul;54(1):68-77. doi: 10.1111/apt.16392. Epub 2021 May 11.
Variants in multiple genetic loci modify the risk of non-alcoholic fatty liver disease (NAFLD) and cirrhosis but there are limited data on the quantitative impact of variant copies on liver fibrosis.
To investigate the effect of PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 genotype on liver fibrosis assessed by magnetic resonance elastography (MRE), a reproducible, accurate, continuous biomarker of liver fibrosis.
This is a cross-sectional analysis derived from a well-characterised cohort at risk for NAFLD who underwent genotyping and MRE assessment. Liver stiffness (LS) was estimated using MRE and advanced fibrosis was defined as liver stiffness ≥3.63 kilopascals (kPa). Univariable and multivariable linear and logistic regression analysis, were used to assess the association between genotype and MRE.
Two hundred sixty-four patients (63% women) with a mean age 53 (±17) years, and 31% Hispanic ethnicity with genotyping and MRE were included. The odds of advanced fibrosis were 3.1 (95% CI: 1.1-8.9, P = 0.04) for CG and 6.5 (95% CI: 2.2-18.9, P < 0.01) for GG compared to CC PNPLA3 genotype. Each PNPLA3 risk variant copy was associated with 0.40 kPa (95% CI: 0.19-0.61, P < 0.01) increase in LS on MRE in analysis adjusted for age, sex and BMI and there was significant genotype-age interaction (P < 0.01). Conversely, the protective TA allele in HSD17B13 was associated with a -0.41 kPa (95% CI: -0.76 to -0.05, P = 0.03) decrease in liver stiffness on MRE multivariable analysis.
Knowledge of PNPLA3 and HSD17B13 genotype may assist in the non-invasive risk stratification of NAFLD with closer monitoring recommended for those with high genetic risk.
多个遗传位点的变异可改变非酒精性脂肪性肝病（NAFLD）和肝硬化的风险，但关于变异拷贝数对肝纤维化的定量影响的数据有限。
研究磁共振弹性成像（MRE）评估的 PNPLA3、TM6SF2、MBOAT7、GCKR 和 HSD17B13 基因型对肝纤维化的影响，MRE 是一种可重复性好、准确、连续的肝纤维化生物标志物。
这是一项来自于具有非酒精性脂肪性肝病风险的特征明确队列的横断面分析，该队列进行了基因分型和 MRE 评估。使用 MRE 估计肝硬度（LS），并将晚期纤维化定义为 LS≥3.63 千帕斯卡（kPa）。采用单变量和多变量线性和逻辑回归分析，评估基因型与 MRE 之间的关联。
共纳入 264 例患者（63%为女性），平均年龄 53（±17）岁，31%为西班牙裔，进行了基因分型和 MRE 检查。与 CC 基因型相比，CG 和 GG 基因型的 PNPLA3 基因型发生晚期纤维化的几率分别为 3.1（95%CI：1.1-8.9，P=0.04）和 6.5（95%CI：2.2-18.9，P<0.01）。在调整年龄、性别和 BMI 后，MRE 上每一个 PNPLA3 风险变异拷贝与 LS 增加 0.40 kPa（95%CI：0.19-0.61，P<0.01）相关，并且存在显著的基因型-年龄交互作用（P<0.01）。相反，HSD17B13 中的保护性 TA 等位基因与 MRE 多变量分析中 LS 减少 0.41 kPa（95%CI：-0.76 至-0.05，P=0.03）相关。
PNPLA3 和 HSD17B13 基因型的知识可能有助于非酒精性脂肪性肝病的非侵入性风险分层，对于遗传风险较高的患者，建议进行更密切的监测。
