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非酒精性脂肪肝基因多态性及其与CK-18、Fetuin B水平相关性研究
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注册号:

Registration number:

ChiCTR1800015426 

最近更新日期:

Date of Last Refreshed on:

2018-03-31 

注册时间:

Date of Registration:

2018-03-28 

注册号状态:

预注册  

Registration Status:

Prospective registration  

注册题目:

非酒精性脂肪肝基因多态性及其与CK-18、Fetuin B水平相关性研究 

Public title:

The association of NAFLD-related gene polymorphisms and the levels of CK-18 and Fetuin B  

注册题目简写:

 

English Acronym:

 

研究课题的正式科学名称:

非酒精性脂肪肝基因多态性及其与CK-18、Fetuin B水平相关性研究 

Scientific title:

The association of NAFLD-related gene polymorphisms and the levels of CK-18 and Fetuin B  

研究课题代号(代码):

Study subject ID:

 

在二级注册机构或其它机构的注册号:

The registration number of the Partner Registry or other register:

 

申请注册联系人:

刘守胜 

研究负责人:

辛永宁 

Applicant:

Shousheng Liu 

Study leader:

Yongning Xin 

申请注册联系人电话:

Applicant telephone:

+86 18765236844 

研究负责人电话:

Study leader's telephone:

+86 0532-82789463 

申请注册联系人传真 :

Applicant Fax:

 

研究负责人传真:

Study leader's fax:

 

申请注册联系人电子邮件:

Applicant E-mail:

shoushengliuouc@163.com 

研究负责人电子邮件:

Study leader's E-mail:

xinyongning@163.com 

申请单位网址(自愿提供):

Applicant website(voluntary supply):

 

研究负责人网址(自愿提供):

Study leader's website(voluntary supply):

 

申请注册联系人通讯地址:

山东省青岛市市南区东海中路5号青岛市市立医院 

研究负责人通讯地址:

山东省青岛市市北区胶州路1号青岛市市立医院 

Applicant address:

Qingdao Municipal Hospital, 5 Donghai Zhong Road, Qingdao, Shandong, China 

Study leader's address:

Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong, China 

申请注册联系人邮政编码:

Applicant postcode:

 

研究负责人邮政编码:

Study leader's postcode:

 

申请人所在单位:

青岛市市立医院 

Applicant's institution:

Qingdao Municipal Hospital 

是否获伦理委员会批准:

是 

Approved by ethic committee:

Yes 

伦理委员会批件文号:

Approved No. of ethic committee:

2017-20 

伦理委员会批件附件:

Approved file of Ethical Committee:

查看附件View

批准本研究的伦理委员会名称:

青岛市市立医院医学伦理委员会 

Name of the ethic committee:

ethical committee of Qingdao municipal hospital 

伦理委员会批准日期:

Date of approved by ethic committee:

 

伦理委员会联系人:

代旭东 

Contact Name of the ethic committee:

Xudong Dai 

伦理委员会联系地址:

青岛市市北区胶州路1号 

Contact Address of the ethic committee:

1 Jiaozhou Road, Qingdao, Shandong, China 

伦理委员会联系人电话:

Contact phone of the ethic committee:

 

伦理委员会联系人邮箱:

Contact email of the ethic committee:

 

研究实施负责(组长)单位:

青岛市市立医院 

Primary sponsor:

Qingdao Municipal Hospital 

研究实施负责(组长)单位地址:

山东省青岛市市北区胶州路1号 

Primary sponsor's address:

1 Jiaozhou Road, Qingdao, Shandong, China 

试验主办单位(项目批准或申办者):

Secondary sponsor:

国家:

中国

省(直辖市):

山东省

市(区县):

青岛市

Country:

China

Province:

Shandong

City:

Qingdao

单位(医院):

青岛市市立医院

具体地址:

山东省青岛市市北区胶州路1号

Institution
hospital:

Qingdao Municipal Hospital

Address:

1 Jiaozhou Road, Qingdao, Shandong, China

经费或物资来源:

国家和省市级课题 

Source(s) of funding:

The funding of National, provincial and municipal projects. 

研究疾病:

非酒精性脂肪性肝病 

Target disease:

Non-alcoholic fatty liver disease 

研究疾病代码:

 

Target disease code:

 

研究类型:

诊断试验 

Study type:

Diagnostic test 

研究所处阶段:

其它 

Study phase:

N/A 

研究目的:

(1)本课题拟通过“个体”水平对TM6SF2基因、LIPA基因、PNPLA3基因、TRIB1基因、MBOAT7基因、卵磷脂胆固醇酰基转移酶(LCAT)、GCKR基因、PCSK9基因、FADS2基因、DPP4基因、FABP2基因及USF1基因多态性在NAFLD 合并冠心病的发生发展中的相关性和可能的作用机制进行探讨。 (2)本课题有利于明确TM6SF2基因、LIPA基因、PNPLA3基因、TRIB1基因、MBOAT7基因、卵磷脂胆固醇酰基转移酶(LCAT)、GCKR、基因、PCSK9基因、FADS2基因、DPP4基因、FABP2基因及USF1基因的多态性在NAFLD合并冠心病的个体中的功能意义,有利于识别和干预高危易感人群,更有利于NAFLD的防治研究,实现真正意义上的个体化治疗。 (3)测定CK18(细胞角蛋白18)、Fetuin B在NAFLD合并冠心病的患者血清中的水平,明确冠心病的获得是否对NAFLD患者血清CK18水平产生影响,同时对合并冠心病的NAFLD患者肝脏病变程度进行分级,明确该因子与NAFLD进展过程中炎症分级、纤维化及脂肪变程度的关系。 

Objectives of Study:

(1) This study aims to investigate the association and underlying mechanism of genes polymorphisms of TM6SF2, LIPA, PNPLA3, TRIB1, MBOAT7, LCAT, GCKR, PCSK9, FADS2, DPP4, FABP2, and USF1 with the risk of NAFLD combined CVD in individuals. (2) This study could illuminate the function of genes polymorphisms of TM6SF2, LIPA, PNPLA3, TRIB1, MBOAT7, LCAT, GCKR, PCSK9, FADS2, DPP4, FABP2, and USF1 in patients with NAFLD combined CVD. This study is beneficial to recognize and intervene the high risk and susceptible population, is helpful to the prophylaxis and treatment of NAFLD. This make for the realization of individualized treatment. (3) To investigate the relationship of CVD and the serum CK18 levels of NAFLD patients, the serum levels of CK18 and Fetuin B in patients with NAFLD combined CVD would be measured. The degree of liver lesion will be graded in the patients with NAFLD and CVD, clarify the association of serum CK18 levels with the inflammation grading, fibrosis and steatosis degrees in the NAFLD progression.  

药物成份或治疗方案详述:

 

Description for medicine or protocol of treatment in detail:

 

研究设计:

诊断性病例对照试验 

Study design:

Diagnostic test: case-control 

纳入标准:

NAFLD患者纳入标准: 同时满足临床诊断+病理诊断或影像学诊断,即可诊断为NAFLD。 临床诊断: 临床诊断必须满足以下所有条件: 1)既往无饮酒史或者饮酒折合成的酒精含量<140g/week(女性<70g/week); 2)既往不存在可以导致脂肪肝的疾病史,包括自身免疫性肝病(Autoimmune liver disease)、药物性肝损伤(DILI)、病毒性肝炎(如乙型、丙型等)、等其他的疾病。 3)在原发病的基础上,尚存在乏力、恶心、呕吐、食欲减退、肝区疼痛及肝脾肿大等非特殊性的临床表现。 4)出现MetS相关组分,如肥胖、糖耐量减低(IGT)、血脂代谢紊乱、高血压,高血粘稠度,高尿酸血症(UA),高胰岛素血症等等。 5)无法解释的血清谷丙转移酶(ALT)、谷草转移酶(AST)、γ- 谷氨酰转移酶(GGT)轻至中度升高超过六个月,以ALT为主。 病理诊断: 肝活检病理学诊断需符合脂肪肝的病理诊断标准,如肝脏细胞实质大泡性脂肪变、气球样变、扩散性肝小叶轻度炎症等等。 影像学诊断: 腹部肝脏超声表现需符合弥漫性脂肪肝的诊断标准,即满足以下任意两项即可: 1)肝脏回声在近场处强于肾脏或脾脏,呈“明亮肝”; 2)在远场处肝脏回声越发变弱或消退; 3)肝脏的内部管道结构显示欠佳。 本实验中的中度至重度NAFLD患者主要以影像学为主要依据: 1)肝脏回声在近场处是强于肾脏或脾脏,呈“明亮肝”; 2)在远场处肝脏回声越发变弱或消退; 3)肝脏的内部管道结构显示欠佳; 4)肝脏轻--中度肿大,边缘角圆钝; 5)彩色多普勒血流仪器显示肝脏内血流信号减少或无; 6)肝脏右叶包膜以及横膈回声显示欠佳或者不完整。 同时满足1)+2)及3)~5)中任意一项者为轻度脂肪肝;同时满足1)+2)及3)~5)中任意两项者为中度脂肪肝;同时满足1)+2)+6)及3)~5)中任意两项者为重度脂肪肝。 NAFLD合并冠心病患者的纳入标准: 1)经冠状动脉造影(狭窄≥50%)确诊为冠心病的患者 2)同时满足NAFLD诊断标准的患者; 健康对照组的纳入标准: 健康对照组的全数受试者则为在经过排除曾经患有一些疾病既往史的前提下进行详细的病史询问、专业的体格检查以及一些必要的实验室以及影像学检查后最终确定的正常的汉族人群。 单纯冠心病组纳入标准: 单纯冠心病组的全数受试者均为经冠状动脉造影(狭窄≥50%)确诊为冠心病的患者,排除曾经患有一些疾病既往史的前提下进行详细的病史询问、专业的体格检查以及一些必要的实验室以及影像学检查后最终确定的未合并NAFLD的单纯冠心病患者。 

Inclusion criteria

NAFLD inclusion criteria: The patients could be diagnosed with NAFLD when at least two symptoms (clinical diagnosis, pathological diagnosis, and imaging diagnosis) are observed. Clinical diagnosis 1. NAFLD patients inclusion criteria: 1) No history of alcohol or the alcohol intakes < 140g/week (female < 70g/week) in the past; 2) There is not diseases history which could result in the fatty liver, including autoimmune liver disease, DILI, or viral hepatitis and other diseases; 3) Based on the protopathy, there are some non-specific clinical manifestation, such as weak, nausea, emesis, anorexia, hepatalgia, and hepatosplenomegaly; 4) Appear the MetS-related component, such as obesity, IGT, lipid metabolism disorder, high blood pressure, high blood viscosity, UA, and hyperinsulinemia; 5) Inexplainable increased levels of serum ALT, AST, and GGT over 6 months, Pathological diagnosis Biopsy pathological diagnosis must accord with the pathological diagnosis standard of NAFLD, such as the liver cell parenchymal fat change, ballooning change, and diffuse mild inflammation of hepatic lobule. Imaging diagnosis: Abdominal hepatic ultrasonography must accord with the standard of diffusibility fatty liver. 1) Liver echo are stronger in near field than kidney and spleen, be the bright liver; 2) Liver echo becomes week or fade away in the far field; 3) The internal pipeline structures of liver are unnormal. CVD inclusion criteria: All the subjects should be the CVD patients which are confirmed by the coronary arteriography (stenosis ≥ 50%), exclude some diseases history, and inquiry the detailed diseases history, do the professional physical examination, and some essential laboratorial and imaging examination, to exclude the NAFLD patients. NAFLD combine CVD inclusion criteria: 1) Patients that are diagnosed as the CVD by coronary arteriography (stenosis ≥ 50%); 2) CVD patients that meet the NAFLD diagnose standard; Healthy control inclusion criteria: All the subjects must exclude some diseases history, and inquiry the detailed diseases history, do the professional physical examination, and some essential laboratorial and imaging examination, to confirm the healthy physical condition. 

排除标准:

NAFLD患者的排除标准: 1)排除能够导致脂肪肝其他的肝脏疾病,自身免疫性肝病(Autoimmune liver disease)、药物性肝损伤(DILI)、病毒性肝炎(慢性乙型、丙型等)等其他的疾病。 2)排除既往或者正罹患肝恶性肿瘤、胆道感染等疾病,及目前或者近期曾经服用过可能导致血清肝脏功能相关的转氨酶酶谱(ALT、AST、GGT等)异常的药物。 3)排除患有严重器质性疾病,如心脏病,以及恶性肿瘤的病人。 4)排除既往有长期大量饮酒史患者,男性乙醇摄入量>140g/week(女性>70g/week), 5)研究人员认为不适合参与该研究的患者 6)不能够定期随访的患者; 

Exclusion criteria:

NAFLD patients exclusion criteria: 1) Exclude the other liver diseases that could result in the fatty liver, including autoimmune liver disease, DILI, or viral hepatitis and other diseases; 2) Exclude the subjects that suffering or suffered the malignant tumor, and the infection of biliary tract. Exclude the subjects that have taken the medicines which could result in the disorder of the serum levels of ALT, AST, GGT recently; 3) Exclude the subjects that suffering the serious organic disease, such as heart disease and malignant tumor; 4) Exclude the subjects that drunk for a long time in the past, and the alcohol intake in male >140g/week (female > 70g/week); 5) Exclude the subjects that do not suit for the standard of researcher; 6) Exclude the subjects that could not follow-up visit at regular intervals.  

研究实施时间:

Study execute time:

From2019-01-01To 2019-12-31 

征募观察对象时间:

Recruiting time:

From2018-06-01To 2019-06-30 

诊断试验:

Diagnostic Tests:

金标准或参考标准(即可准确诊断某疾病的单项方法或多项联合方法,在本研究中用于诊断是否有该病的临床参考标准):

肝活检,超声检测,冠状动脉造影

Gold Standard or Reference Standard (The clinical reference standards required to establish the presence or absence of the target condition in the tested population in present study):

Biopsy;B-type ultrasonography;coronary arteriography

指标试验(即本研究的待评估诊断试验,无论为方法、生物标志物或设备,均请列出名称):

单核苷酸多态性

Index test:

single nucleotide polymorphism

目标人群(可以是某种疾病患者或正常人群,详细描述其疾病特征,注意应纳入符合分布特点的全序列病例,具有良好的代表性)

NAFLD患者; NAFLD合并冠心病患者;

例数:

Sample size:

800

Target condition (The target condition is a particular disease or disease stage that the index test will be intended to identify. Please specify the characteristics in detail; the population should has a complete spectrum and good representative):

NALD, and NDLD complicated with CVD patients

容易混淆的疾病人群(即与目标疾病不易区分的一种或多种不同疾病,应避免采用正常人群对照的病例-对照设计):

健康对照

例数:

Sample size:

0

Population with condition difficult to distinguish from the target condition, the normal population in a case-control study design should be avoid:

health population

研究实施地点:

Countries of recruitment and research settings:

国家:

中国 

省(直辖市):

山东 

市(区县):

青岛 

Country:

China 

Province:

Shandong 

City:

Qingdao 

单位(医院):

青岛市市立医院 

单位级别:

三甲医院 

Institution
hospital:

Qingdao Municipal Hospital  

Level of the institution:

Tertiary A Hospital 

测量指标:

Outcomes:

指标中文名:

TM6SF2rs58542926 基因多态性

指标类型:

主要指标 

Outcome:

TM6SF2 rs58542926 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

LCAT基因rs3729639、rs5922位点多态性

指标类型:

主要指标 

Outcome:

LCAT rs3729639, rs5922 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

LIPA基因rs1051338、rs1412444位点多态性

指标类型:

主要指标 

Outcome:

LIPA rs1051338, rs1412444 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

PNPLA3 rs734809基因多态性

指标类型:

主要指标 

Outcome:

PNPLA3 rs734809 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

TRIB1 rs17321515,rs2954029基因多态性

指标类型:

主要指标 

Outcome:

TRIB1 rs17321515, rs2954029 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

MBOAT7 rs641738 基因多态性

指标类型:

主要指标 

Outcome:

MBOAT7 rs641738 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

GCKR rs1260326和rs780094基因多态性

指标类型:

主要指标 

Outcome:

GCKR rs1260326, rs780094 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

PCSK9 rs505151基因多态性

指标类型:

主要指标 

Outcome:

PCSK9 rs505151 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

FADS2 rs3834458、rs66698963基因多态性

指标类型:

主要指标 

Outcome:

FADS2 rs3834458, rs66698963 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

DPP4 rs1558957、rs17848915、rs7608798基因多态性

指标类型:

主要指标 

Outcome:

DPP4 rs1558957, rs17848915、rs7608798 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

FABP2 rs1799883基因多态性

指标类型:

主要指标 

Outcome:

FABP2 rs1799883 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

USF1 rs6427573基因多态性

指标类型:

主要指标 

Outcome:

USF1 rs6427573 polymorphism

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血清CK-18水平

指标类型:

主要指标 

Outcome:

serum CK-18 level

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

指标中文名:

血清Fetuin B水平

指标类型:

主要指标 

Outcome:

serum Fetuin B level

Type:

Primary indicator 

测量时间点:

测量方法:

Measure time point of outcome:

Measure method:

采集人体标本:

Collecting sample(s)
from participants:

标本中文名:

血液

组织:

Sample Name:

Blood

Tissue:

人体标本去向

使用后销毁 

说明

Fate of sample:

Destruction after use 

Note:

征募研究对象情况:

Recruiting status:

尚未开始

Not yet recruiting

年龄范围:

Participant age:

最小 Min age years
最大 Max age years

性别:

男女均可

Gender:

Both

随机方法(请说明由何人用什么方法产生随机序列):

N/A

Randomization Procedure (please state who generates the random number sequence and by what method):

N/A

盲法:

Blinding:

试验完成后的统计结果(上传文件):

Calculated Results after
the Study Completed(upload file):

是否共享原始数据:

IPD sharing

是Yes

共享原始数据的方式(说明:请填入公开原始数据日期和方式,如采用网络平台,需填该网络平台名称和网址):

2020年12月之前通过发表论文的形式进行公开

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url):

We will sharing the metadata by published papers before the December, 2020.

数据采集和管理(说明:数据采集和管理由两部分组成,一为病例记录表(Case Record Form, CRF),二为电子采集和管理系统(Electronic Data Capture, EDC),如ResMan即为一种基于互联网的EDC:

病理记录表

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture:

Case Record Form

数据与安全监察委员会:

Data and Safety Monitoring Committee:

暂未确定/Not yet

注册人:

Name of Registration:

 2018-03-28
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