对NTCP（SLC10A1）的rs2296651（S267F）的变体是成反比与慢性乙型

StephenW

                    
Gut doi:10.1136/gutjnl-2015-310686

    GI cancer

    Original article

The rs2296651 (S267F) variant on NTCP (SLC10A1) is inversely associated with chronic hepatitis B and progression to cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B

    Hui-Han Hu1, Jessica Liu1, Yu-Ling Lin1, Wun-Sheng Luo1, Yu-Ju Chu1, Chia-Lin Chang1, Chin-Lan Jen1, Mei-Hsuan Lee2, Sheng-Nan Lu3, Li-Yu Wang4, San-Lin You1, Hwai-I Yang1,2, Chien-Jen Chen1,5, for the REVEAL-HBV Study Group

    1Genomics Research Center, Academia Sinica, Taipei, Taiwan
    2Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
    3Department of Gastroenterology, Chang-Gung Memorial Hospital, Kaohsiung, Taiwan
    4Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
    5Graduate Institute of Epidemiology and Preventative Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

    Correspondence to Dr Hwai-I Yang, Genomics Research Center, Academia Sinica, 128 Academia Road Section 2, Nankang, Taipei 11529, Taiwan; hiyang{at}gate.sinica.edu.tw

    Received 7 September 2015
    Revised 7 November 2015
    Accepted 9 November 2015
    Published Online First 7 December 2015

Abstract

Objective The sodium taurocholate co-transporting polypeptide (NTCP), encoded by SLC10A1, was recently identified as a receptor for HBV. We assessed the association of the p.Ser267Phe variant (rs2296651) with chronic hepatitis B (CHB) serostatus, cirrhosis and hepatocellular carcinoma (HCC) in patients with CHB.

Design The variant was genotyped in 3801 patients with CHB and 3801 matched hepatitis B surface antigen (HBsAg) seronegative individuals. ORs with 95% CIs for the variant's association with CHB, cirrhosis and HCC were estimated using logistic regression.

Results In patients with CHB, the S267F variant was observed in 515 (18.5%) controls, 40 (17.2%) cirrhosis only cases, 49 (13.2%) non-cirrhotic HCC cases, and 52 (12.7%) cirrhotic-HCC cases. After adjustment for known risk factors, S267F was significantly associated with decreased risk for cirrhosis (OR 0.65 (95% CI 0.49 to 0.86), p=0.002) and HCC (OR 0.55 (95% CI 0.42 to 0.72), p<0.001). This association persisted for non-cirrhotic and cirrhotic-HCC. Compared with patients with HBV DNA levels greater than 105 copies/mL who carried the GG genotype, patients who had undetectable HBV DNA and the GA or AA genotypes had a 25-fold decreased risk of developing HCC (OR 0.04 (95% CI 0.02 to 0.11), p<0.001). The AA genotype was also associated with HBsAg seronegativity (OR 0.13 (95% CI 0.05 to 0.34), p<0.001).

Conclusions The SLC10A1 (NTCP) S267F variant is independently associated with decreased risk of cirrhosis and HCC, and resistance to CHB infection. Together with serum HBV DNA levels, S267F may help to identify patients with CHB with very low risk of HCC.


                           

StephenW

肠道DOI：10.1136 / gutjnl-2015-310686

    胃肠道癌

    原创文章

对NTCP（SLC10A1）的rs2296651（S267F）的变体是成反比与慢性乙型肝炎发展为肝硬化和肝癌患者的慢性乙肝相关

    惠汉HU1，杰西卡Liu1，玉玲琳，青云盛Luo1，俞菊Chu1，嘉莲Chang1，金澜Jen1，梅轩Lee2，盛楠LU3，李渝Wang4，基于SAN林You1，Hwai-I Yang1,2，陈建仁Chen1,5，为REVEAL-HBV研究小组

    1Genomics研究中心，中央研究院，台北，台湾
    临床医学，国立阳明大学，台北，台湾2中国科学院
    消化内科，长庚纪念医院，高雄，台湾3Department
    4Department医学，马偕医学院，新北市，台湾
    流行病学5Graduate学院预防医学，公共卫生，国立台湾大学学院，台北，台湾

    函授博士Hwai-I扬，基因组学研究中心，中央研究院，中国科学院128号第2，南港，台北11529，台湾; hiyang {}在gate.sinica.edu.tw

    收到的2015年7月
    经修订的2015年7月
    接受2015年9月
    网上公布的前7 2015年12月

抽象

客观的牛磺胆酸钠共转运多肽（NTCP），由SLC10A1编码，最近被确定为受体乙肝病毒。我们评估了p.Ser267Phe变种（rs2296651）与慢性乙型肝炎（CHB）血清状况，肝硬化和肝细胞癌（HCC）的慢性乙肝患者的关联。

设计的变体基因分型在3801 CHB患者和3801匹配的乙肝表面抗原（HBsAg）阴性个体。 OR值和95％可信区间为慢性乙型肝炎，肝硬化和肝癌变异的关联采用Logistic回归估算。

结果在慢性乙肝患者中，S267F变异观察515（18.5％）的控制，40（17.2％），肝硬化只的情况下，49（13.2％），非肝硬化肝癌的情况下，和52（12.7％），肝硬化，肝癌病例。调整已知危险因素后，S267F是显著与风险降低肝硬化（OR 0.65（95％CI为0.49〜0.86），P = 0.002）和肝癌相关​​（OR 0.55（95％CI为0.42〜0.72），P <0.001） 。该协会坚持了非肝硬化和肝硬化，肝癌。与患者的HBV DNA水平相比大于105拷贝/毫升谁携带GG基因型，谁曾检测不到HBV DNA和GA或AA基因型有25倍的降低发生HCC（或0.04（95％CI为0.02〜危险的病人0.11），P <0.001）。 AA基因型也与乙肝表面抗原血清阴性（OR 0.13（95％CI为0.05〜0.34），P <0.001）。

结论SLC10A1（NTCP）S267F的变体独立地与肝硬化及肝细胞癌，和耐CHB感染的风险降低。加上血清HBV DNA水平，S267F可能有助于发现慢性乙肝患者肝癌的风险非常低。

zgct

谢谢