MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals.
MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals.
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DOI：
10.1038/s41598-017-04991-0
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发表时间：
2017-07-03
影响因子：
4.6
通讯作者：
Valenti L
中科院分区：
文献类型：
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作者：
Donati B;Dongiovanni P;Romeo S;Meroni M;McCain M;Miele L;Petta S;Maier S;Rosso C;De Luca L;Vanni E;Grimaudo S;Romagnoli R;Colli F;Ferri F;Mancina RM;Iruzubieta P;Craxi A;Fracanzani AL;Grieco A;Corradini SG;Aghemo A;Colombo M;Soardo G;Bugianesi E;Reeves H;Anstee QM;Fargion S;Valenti L
非酒精性脂肪性肝病（NAFLD）是肝细胞癌（HCC）的一个新兴病因，尤其是在非肝硬化个体中。rs641738 C > T MBOAT7/TMC4变异易致进行性NAFLD，但其对肝癌发生的影响尚不清楚。在意大利NAFLD患者中，rs641738 T等位基因与NAFLD- hcc相关（OR 1.65, 1.08-2.55; n = 765），特别是在没有晚期纤维化的患者中（p < 0.001）。风险T等位基因与MBOAT7的3 ' -UTR变异和无严重纤维化患者的MBOAT7表达降低有关。PNPLA3、TM6SF2和MBOAT7危险变异的数量独立于临床因素与NAFLD-HCC相关（p < 0.001），但没有显著提高其预测准确性。当结合来自独立的英国NAFLD队列的数据时，在非肝硬化患者（n = 913,41例HCC患者）的整体队列中，T等位基因仍然与HCC相关（OR 2.10, 1.33-3.31）。最后，在合并慢性丙型肝炎或酒精性肝病的非肝硬化患者队列中（n = 1121）， T等位基因与HCC风险独立相关（or 1.93, 1.07-3.58）。总之，MBOAT7 rs641738 T等位基因与MBOAT7表达降低相关，并可能在无肝硬化患者中易患HCC，提示应在未来旨在分层NAFLD-HCC风险的前瞻性研究中对其进行评估。
Nonalcoholic fatty liver disease (NAFLD) represents an emerging cause of hepatocellular carcinoma (HCC), especially in non-cirrhotic individuals. The rs641738 C > T MBOAT7/TMC4 variant predisposes to progressive NAFLD, but the impact on hepatic carcinogenesis is unknown. In Italian NAFLD patients, the rs641738 T allele was associated with NAFLD-HCC (OR 1.65, 1.08–2.55; n = 765), particularly in those without advanced fibrosis (p < 0.001). The risk T allele was linked to 3’-UTR variation in MBOAT7 and to reduced MBOAT7 expression in patients without severe fibrosis. The number of PNPLA3, TM6SF2, and MBOAT7 risk variants was associated with NAFLD-HCC independently of clinical factors (p < 0.001), but did not significantly improve their predictive accuracy. When combining data from an independent UK NAFLD cohort, in the overall cohort of non-cirrhotic patients (n = 913, 41 with HCC) the T allele remained associated with HCC (OR 2.10, 1.33–3.31). Finally, in a combined cohort of non-cirrhotic patients with chronic hepatitis C or alcoholic liver disease (n = 1121), the T allele was independently associated with HCC risk (OR 1.93, 1.07–3.58). In conclusion, the MBOAT7 rs641738 T allele is associated with reduced MBOAT7 expression and may predispose to HCC in patients without cirrhosis, suggesting it should be evaluated in future prospective studies aimed at stratifying NAFLD-HCC risk.