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Abstract：
UNASSIGNED: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD.
UNASSIGNED: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines.
UNASSIGNED: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL.
UNASSIGNED: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk.
UNASSIGNED: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis.
UNASSIGNED: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines.
UNASSIGNED: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL.
UNASSIGNED: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk.
UNASSIGNED: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis.
摘要：
未经证实：酒精相关性肝病（ALD）的进展是由遗传易感性驱动的。脂蛋白脂肪酶（LPL）基因中的rs13702变体与非酒精性脂肪肝疾病有关。我们旨在阐明其在ALD中的作用。
未经证实：酒精相关性肝硬化患者，有（n=385）和无肝细胞癌（HCC）（n=656），肝癌可归因于病毒性丙型肝炎（n=280），酒精滥用而无肝脏损害的对照（n=366），和健康对照(n=277)进行LPLrs13702多态性的基因分型。此外，对英国生物银行队列进行了分析.在人肝标本和肝细胞系中研究LPL表达。
UNASSIGNED：与无HCC的ALD相比，有HCC的ALD中LPLrs13702CC基因型的频率较低（3.9％vs.9.3%）和验证队列（4.7%与9.5%；各p<0.05），与病毒性HCC患者（11.4%）相比，酒精滥用无肝硬化(8.7%)，或健康对照（9.0%）。这种保护作用（比值比[OR]=0.5）在多变量分析中得到证实，包括年龄（OR=1.1/年），男性（OR=3.0），糖尿病（OR=1.8），并携带PNPLA3I148M风险变体(OR=2.0)。在英国生物银行队列中，LPLrs13702C等位基因被复制为HCC的危险因素.LPLmRNA的肝脏表达依赖于LPLrs13702基因型，与对照组和酒精相关的HCC相比，ALD肝硬化患者的肝脏表达明显更高。尽管肝细胞系显示可忽略的LPL蛋白表达,肝星状细胞和肝窦内皮细胞表达LPL。
未经证实：酒精相关性肝硬化患者肝脏中LPL上调。LPLrs13702高生产者变体在ALD中赋予对HCC的保护，这可能有助于对人们进行HCC风险分层。
UASSIGNED：肝细胞癌是受遗传易感性影响的肝硬化的严重并发症。我们发现，编码脂蛋白脂肪酶的基因中的遗传变异可降低酒精相关性肝硬化中患肝细胞癌的风险。这种遗传变异可能直接影响肝脏,因为,与健康的成人肝脏不同，脂蛋白脂肪酶是由酒精相关肝硬化的肝细胞产生的。
未经证实：酒精相关性肝硬化患者，有（n=385）和无肝细胞癌（HCC）（n=656），肝癌可归因于病毒性丙型肝炎（n=280），酒精滥用而无肝脏损害的对照（n=366），和健康对照(n=277)进行LPLrs13702多态性的基因分型。此外，对英国生物银行队列进行了分析.在人肝标本和肝细胞系中研究LPL表达。
UNASSIGNED：与无HCC的ALD相比，有HCC的ALD中LPLrs13702CC基因型的频率较低（3.9％vs.9.3%）和验证队列（4.7%与9.5%；各p<0.05），与病毒性HCC患者（11.4%）相比，酒精滥用无肝硬化(8.7%)，或健康对照（9.0%）。这种保护作用（比值比[OR]=0.5）在多变量分析中得到证实，包括年龄（OR=1.1/年），男性（OR=3.0），糖尿病（OR=1.8），并携带PNPLA3I148M风险变体(OR=2.0)。在英国生物银行队列中，LPLrs13702C等位基因被复制为HCC的危险因素.LPLmRNA的肝脏表达依赖于LPLrs13702基因型，与对照组和酒精相关的HCC相比，ALD肝硬化患者的肝脏表达明显更高。尽管肝细胞系显示可忽略的LPL蛋白表达,肝星状细胞和肝窦内皮细胞表达LPL。
未经证实：酒精相关性肝硬化患者肝脏中LPL上调。LPLrs13702高生产者变体在ALD中赋予对HCC的保护，这可能有助于对人们进行HCC风险分层。
UASSIGNED：肝细胞癌是受遗传易感性影响的肝硬化的严重并发症。我们发现，编码脂蛋白脂肪酶的基因中的遗传变异可降低酒精相关性肝硬化中患肝细胞癌的风险。这种遗传变异可能直接影响肝脏,因为,与健康的成人肝脏不同，脂蛋白脂肪酶是由酒精相关肝硬化的肝细胞产生的。
