| 王立芹,郭维恒,郭志旺,秦璞,张蕊,朱晓敏,刘殿武.PNPLA3、TM6SF2基因多态性及其与吸烟、饮酒交互作用对HBV相关肝癌的影响[J].Chinese journal of Epidemiology,2018,39(12):1611-1616 |
| PNPLA3、TM6SF2基因多态性及其与吸烟、饮酒交互作用对HBV相关肝癌的影响 |
| Effects of PNPLA3, TM6SF2 gene polymorphisms and its interactions with smoking and alcohol drinking on hepatitis B virus-associated hepatocellular carcinoma |
| Received:June 19, 2018 |
| DOI：10.3760/cma.j.issn.0254-6450.2018.12.014 |
| KeyWord: 乙型肝炎病毒 肿瘤,肝 patatin样磷脂酶域3 6号跨膜超家族成员2 交互作用 |
| English Key Word: Hepatitis B virus Carcinoma, hepatocellular Patatin-like phospholipase domain containing 3 Transmembrane 6 superfamily member 2 Interaction effect |
| FundProject:河北省自然基金重大项目（H2016206576） |
| Author Name | Affiliation | E-mail | | Wang Liqin | Hebei Key Laboratory of Environment and Population Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang 050031, China | | | Guo Weiheng | Hebei Key Laboratory of Environment and Population Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang 050031, China | | | Guo Zhiwang | Hebei Key Laboratory of Environment and Population Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang 050031, China | | | Qin Pu | Hebei Key Laboratory of Environment and Population Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang 050031, China | | | Zhang Rui | Hebei Key Laboratory of Environment and Population Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang 050031, China | | | Zhu Xiaomin | Hebei Key Laboratory of Environment and Population Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang 050031, China | | | Liu Dianwu | Hebei Key Laboratory of Environment and Population Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang 050031, China | liudianw@hebmu.edu.cn |
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| Abstract: |
| 目的 探讨PNPLA3、TM6SF2基因多态性及其与吸烟、饮酒交互作用对HBV相关肝癌（hepatitis B virus-associated hepatocellular carcinoma，HBV-HCC）的影响。方法 收集2010年1月至2014年3月HBV-HCC患者、慢性乙型肝炎（乙肝）患者（CHB）、肝硬化患者（LC）以及健康体检者的血液标本，应用飞行质谱技术检测patatin样磷脂酶域3（PNPLA3）基因位点rs738409和6号跨膜超家族成员2（TM6SF2）基因位点rs58542926的单核苷酸多态性（SNP）。利用在线SNP stats寻找基因多态性的最优赋值方法；检验SNP是否符合哈-温（H-W）遗传平衡定律；采用多分类logistic回归分析PNPLA3和TM6SF2多态性及吸烟、饮酒因素对HBV-HCC的影响，采用叉生分析和二分类logistic回归分析探讨基因-基因、基因-吸烟、饮酒交互作用对HBV-HCC的影响。结果 H-W遗传平衡检验结果显示，CHB组rs738409位点的基因型频率分布不符合H-W遗传平衡定律（χ2=11.980，P<0.005），CHB组rs58542926位点、HBV-HCC组和LC组rs738409和rs58542926位点均符合H-W遗传平衡定律；调整年龄、性别的影响后，与健康体检者相比，HBV-HCC组rs58542926突变的OR=1.659，95% CI：1.026~2.684，P=0.039。与CHB组相比，HBV-HCC组饮酒的OR=1.680，95% CI：1.121~2.519，P=0.012。与LC组相比，HBV-HCC组饮酒与吸烟的OR值（95% CI）分别为1.539（1.071~2.213）和1.453（1.005~2.099）。交互作用分析显示，HBV-HCC组与CHB+LC组相比，rs738409与rs58542926交互作用的叉生分析相加模型OR=1.548（U=1.885，P=0.029），logistic回归相乘模型OR=1.658（P=0.024）；饮酒与rs738409的交互作用叉生分析，饮酒且rs738409突变相加模型OR=1.811（U=1.965，P=0.024），相乘模型无统计学意义；logistic回归相乘模型吸烟与饮酒的交互作用OR=1.756（P<0.001）。结论 TM6SF2基因突变、吸烟、饮酒是HBV-HCC的危险因素，PNPLA3与TM6SF2基因都突变、饮酒并且吸烟是HBV-HCC的危险因素。PNPLA3的单基因突变可以减弱饮酒对HBV-HCC的危害。 |
| English Abstract: |
| Objective To explore the SNP effects of patatin-like phospholipase domain which containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2) gene, environmental effects of smoking, alcohol drinking and interaction between gene-gene, gene-environment and drinking-smoking on hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). Methods We collected anticoagulant peripheral blood from patients of HBV-HCC, chronic hepatitis B (CHB), liver cirrhosis (LC) and from healthy controls to detect the single nucleotide polymorphism (SNP) of patatin-like phospholipase domain containing 3 (PNPLA3) gene loci rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) gene loci rs58542926, using the flight mass spectrometry method. The optimal assignment value of gene polymorphisms was defined by using the online SNP stats. Hardy-Weinberg (H-W) balance was tested for SNP. Effects of the genetic and environmental factors to HBV-HCC were analyzed by using the multiple classification logistic regression method. The gene-gene, gene-smoking and alcohol drinking interaction effects were investigated by Fork-Life analysis and binary logistic regression methods. Results The frequency distribution of CHB group rs738409 loci seemed not in conformity with the H-W balance (χ2=11.980, P<0.005). Two loci frequency distributions in the other groups were all in accordandce with the H-W balance. After adjusting for influences on age and sex and comparing to the healthy group, the rs58542926 mutation appeared as OR=1.659, 95% CI:1.026-2.684, P=0.039, in the HBV-HCC group. When comparing to CHB group, the HBV-HCC group presented that drinking as OR=1.680, 95% CI:1.121-2.519, P=0.012. When comparing to the LC group, the ORs of drinking and smoking were 1.539 (1.071-2.213) and 1.453 (1.005-2.099) respectively, in the HBV-HCC group. When comparing to the CHB+LC group, interactions between the HBV-HCC group were found rs738409 and rs58542926 on additive model OR=1.548 (U=1.885, P=0.029) and OR=1.658 (P=0.024) on logistic regression model while drinking was rs738409 on interaction additive model with OR=1.811(U=1.965, P=0.024). As for drinking and mutation of rs738409, the multiplication model of logistic regression showed no statistically significant differences. Interaction between smoking and drinking appeared as OR=1.756 (P<0.001) in the logistics regression multiplication model. Conclusions Factors as mutation of TM6SF2, smoking and drinking all appeared as risk factors for HBV-HCC. Mutations of both PNPLA3 and TM6SF2, together with smoking and drinking all served as risk factors for HBV-HCC. However, the mutation of single PNPLA3 appeared as a protective factor on HBV-HCC. |
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