PNPLA3基因rs738409位点和TM6SF2基因rs58542926位点的变异增加了酒精性肝硬化患者患肝细胞癌的风险。
PNPLA3 rs738409 and TM6SF2 rs58542926 variants increase the risk of hepatocellular carcinoma in alcoholic cirrhosis.
作者信息
Falleti Edmondo, Cussigh Annarosa, Cmet Sara, Fabris Carlo, Toniutto Pierluigi
机构信息
Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Italy.
Department of Medicine and Pathology Clinical and Experimental, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Italy.
出版信息
Dig Liver Dis. 2016 Jan;48(1):69-75. doi: 10.1016/j.dld.2015.09.009. Epub 2015 Sep 28.
BACKGROUND
PNPLA3 rs738409 polymorphism is associated with fatty liver disease, alcoholic or non-alcoholic (NAFLD) and hepatocellular carcinoma (HCC). TM6SF2 rs58542926 is clearly associated with NAFLD, but it is not clearly associated with HCC. The relationship between TM6SF2 rs58542926 and HCC and the potential synergistic effect of TM6SF2 and PNPLA3 variants in modifying the risk of HCC are not known.
AIM
This study assessed the interaction between PNPLA3 rs738409 and TM6SF2 rs58542926 variants in the conditioning of HCC development.
METHODS
A total of 511 cirrhotic patients (44% alcohol-related, 56% viral, 57.5% liver transplanted) were retrospectively investigated for HCC occurrence. PNPLA3 rs734809 and TM6SF2 rs58542926 were genotyped using restriction fragment length polymorphism and real-time allelic discrimination polymerase chain reaction methods.
RESULTS
Patients with HCC were more likely to be PNPLA3 rs734809 G/G homozygotes (41/150 vs. 60/361, p=0.009) or TM6SF2 rs58542926 C/T-T/T (27/150 vs. 41/361, p=0.044). The presence of either PNPLA3 G/G or TM6SF2*/T identified high-risk genotypes for HCC, which were strongly associated with HCC (64/150 vs. 93/361, p=0.0002). This association was evident in alcohol-related (p=0.0007) but not in viral cirrhosis.
CONCLUSION
TM6SF2 C/T or T/T in conjunction with PNPLA3 G/G variants may be potential genetic risk factors for developing HCC in alcohol-related cirrhosis.
背景
PNPLA3基因rs738409多态性与脂肪性肝病、酒精性或非酒精性脂肪性肝病（NAFLD）以及肝细胞癌（HCC）相关。TM6SF2基因rs58542926与NAFLD明确相关，但与HCC的相关性尚不明确。TM6SF2基因rs58542926与HCC之间的关系以及TM6SF2和PNPLA3变异在改变HCC风险方面的潜在协同作用尚不清楚。
目的
本研究评估PNPLA3基因rs738409和TM6SF2基因rs58542926变异在HCC发生过程中的相互作用。
方法
对511例肝硬化患者（44%与酒精相关，56%与病毒相关，57.5%接受肝移植）进行回顾性研究，以观察HCC的发生情况。采用限制性片段长度多态性和实时等位基因鉴别聚合酶链反应方法对PNPLA3基因rs734809和TM6SF2基因rs58542926进行基因分型。
结果
HCC患者更有可能是PNPLA3基因rs734809的G/G纯合子（41/150 vs. 60/361，p = 0.009）或TM6SF2基因rs58542926的C/T - T/T（27/150 vs. 41/361，p = 0.044）。PNPLA3基因G/G或TM6SF2基因*/T的存在确定了HCC的高危基因型，与HCC密切相关（64/150 vs. 93/361，p = 0.0002）。这种关联在酒精相关性肝硬化中明显（p = 0.0007），但在病毒性肝硬化中不明显。
结论
TM6SF2基因的C/T或T/T与PNPLA3基因的G/G变异相结合可能是酒精相关性肝硬化发生HCC的潜在遗传危险因素。
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