PNPLA3基因I148M多态性与慢性乙型肝炎的相关性

发布时间：2018-12-18 07:26

【摘要】：目的慢性乙型肝炎（Chronic hepatitis B, CHB）已成为一种世界性慢性肝脏疾病。CHB与病毒基因型、年龄、环境因素、宿主因素等因素有关，更认为与遗传因素有密切关系。到现在，国内外许多研究指出PNPLA3基因多态性与NAFLD、酒精性肝病、丙型肝炎等肝脏疾病都有密切关系，然而现在还没有关于PNPL A3基因rs738409多态性与慢性乙型肝炎之间联系的报道研究。鉴于上述原因，在青岛中国汉族人群慢性乙型肝炎患者中我们研究PNPLA3基因rs738409多态性的分布情况，探索青岛地区汉族人群中PNPLA3基因多态性与慢性乙型肝炎的相关性。方法本研究通过病史的采集及生化数据结果的整理，共收集标本349例，其中CHB患者185例和健康对照受试者164例。在CHB组及正常组中，外周血进行DNA提取，采用多聚酶链式反应（PCR）扩增目的基因片段序列及应用基因测序方法检测PNPLA3基因rs738409多态性，通过测序结果确定其基因型和等位基因的分布。CHB组与对照组各基因型是否具有群体代表性通过Hardy-weinbeurg遗传平衡定律分析，非条件Logistic回归分析基因变异及CHB相关因素之间的联系。数据分析应用统计学软件SPSS17.0。结果 rs738409GG、GC和CC3种基因型在CHB组和对照组中均被检出：CHB组GG型占13.0%，GC型占37.8%，CC型占49.2%；对照组GG型占6.7%，GC型占30.5%，，CC型占62.8%，基因型分布差异有统计学意义（P0.05）。CHB组与对照组rs738409等位基因频率差异有统计学意义（P0.05）。其中CHB组rs738409G等位基因占31.9%，高于正常对照组的21.9%；G等位基因患CHB的风险是C等位基因的1.67倍（OR=1.67,95%CI:1.18-2.34, P=0.003）。经混杂因素校正后，Logistic回归模型分析结果显示与与CC纯合子携带者相比，携带危险等位基因G的GG+AG基因型增加慢性乙型肝炎的发生风险，比值比为1.76，95％可信区间为1.13-2.35。进一步说明PNPLA3基因与慢性乙型肝炎的发生有关。结论这研究显示在青岛地区中国汉族人中rs738409G基因增加慢性乙型肝炎的风险性，其作用机制有待进一步研究。
[Abstract]:Objective chronic hepatitis B (Chronic hepatitis B, CHB) has become a worldwide chronic liver disease. CHB is related to virus genotype, age, environmental factors, host factors and so on, and it is considered to be closely related to genetic factors. Up to now, many studies at home and abroad have pointed out that PNPLA3 gene polymorphism is closely related to NAFLD, alcoholic liver disease, hepatitis C and other liver diseases. However, no study has been reported on the association between PNPL A 3 gene rs738409 polymorphism and chronic hepatitis B. In view of the above reasons, we studied the distribution of PNPLA3 gene rs738409 polymorphism in Qingdao Chinese Han population, and explored the correlation between PNPLA3 gene polymorphism and chronic hepatitis B in Qingdao Han population. Methods A total of 349 specimens were collected through the collection of history and biochemical data, including 185 CHB patients and 164 healthy control subjects. In CHB group and normal group, DNA was extracted from peripheral blood, polymerase chain reaction (PCR) was used to amplify the target gene fragment sequence, and PNPLA3 gene rs738409 polymorphism was detected by gene sequencing. The distribution of genotypes and alleles was determined by sequencing. Whether the genotypes of CHB group and control group had population representativeness was analyzed by Hardy-weinbeurg genetic balance law. The relationship between gene variation and CHB related factors by non-conditional Logistic regression analysis. Applied Statistics Software SPSS17.0. for data Analysis Results the genotypes of rs738409GG,GC and CC3 were detected in CHB group and control group. The percentage of GG genotype in CHB group was 13.0% and that of GC type was 37.8%. In control group, GG type accounted for 6.7%, GC type accounted for 30.5% and CC type accounted for 62.8%. There was significant difference in genotype distribution between). CHB group and control group (P0.05). The risk of CHB in CHB group was 1.67 times higher than that in C allele (OR=1.67,95%CI:1.18-2.34, P0. 003). After adjustment for confounding factors, Logistic regression model analysis showed that the GG AG genotype carrying risk allele G increased the risk of chronic hepatitis B compared with that of CC homozygote carriers. The ratio is 1.76% and 95% confidence interval is 1.13-2.35. It is further indicated that PNPLA3 gene is associated with the development of chronic hepatitis B. Conclusion this study suggests that rs738409G gene increases the risk of chronic hepatitis B in Chinese Han population in Qingdao area, and its mechanism needs further study.
【学位授予单位】：泰山医学院
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.62

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