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].中华流行病学杂志,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 |
收稿日期:2018-06-19 出版日期:2018-12-14 |
DOI:10.3760/cma.j.issn.0254-6450.2018.12.014 |
中文关键词: 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 |
英文关键词: Hepatitis B virus Carcinoma, hepatocellular Patatin-like phospholipase domain containing 3 Transmembrane 6 superfamily member 2 Interaction effect |
基金项目:河北省自然基金重大项目(H2016206576) |
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中文摘要: |
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。 |
英文摘要: |
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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