中国汉族人群IL-4基因三个多态位点（rs2227284，rs2243283and rs2243288）的单核苷酸多态性

发布时间：2018-09-07 08:20

【摘要】：背景乙型肝炎病毒（Hepatitis B virus, HBV）感染的后果主要受病毒、宿主和环境三者影响。随着人们对HBV认识逐渐增多，宿主遗传因素对HBV感染的后果的影响亦日渐受到人们的关注，其中细胞因子的基因多态性成为研究热点。多项研究已证明细胞因子的基因多态性与HBV感染慢性化的关系密切。白介素4（Interleukin-4,IL-4）在调节T淋巴细胞亚群的动态平衡中起着关键的作用，而T淋巴细胞亚群失衡可影响人类对治疗性疫苗的应答及人类自身免疫性疾病的易感性。此外，IL-4可抑制γ干扰素（Interferon-γ,IFN-γ）和炎症介质的产生，从而防止炎症对肝脏的损伤。亦有报道称IL-4基因突变时，可能改变其表达及其下游信号，从而增加免疫相关性肝脏疾病的个人易感性。因此其单核苷酸多态性（singlenucleotide polymorphism, SNP）可能与慢性乙型肝炎(chronic hepatitis B,CHB)的发病及临床不同转归相关。目的研究IL-4rs2227284G/T、rs2243283C/G和rs2243288A/G位点SNP与中国汉族人群HBV感染慢性化的关系。方法随机入组501位慢性HBV患者作为病例组，301位急性自限性HBV感染者作为对照组。分别检测病例组及对照组所有入组人员的IL-4基因rs2227284G/T、rs2243283C/G和rs2243288A/G三个位点的SNP，分析两组间的等位基因频率、单体型频率、基因型是否存在差异；分析以上三个位点的不同遗传模型是否存在统计学意义；计算以上三个位点的两两位点间的连锁不平衡系数(D’)。我们所采用的是多重单碱基延伸SNP分型技术(Multiplex SNaPshot technique)。结果 1．rs2227284位点3种基因型TT、GT、GG在病例组的分布频率分别为74.3%、24.3%、1.4%,在对照组分别为76.1%、22.3%、1.6%; rs2243283位点3种基因型CG、CC、GG在病例组的分布频率分别为33.1%、63.3%、3.6%,在对照组分别为30.2%、65.1%、4.7%; rs2243288位点3种基因型GG、GA、AA在病例组的分布频率分别为65.1%、31.5%、3.4%,在对照组分别为66.4%、30.6%、3.0%。χ2检验结果显示, IL-4基因以上3个位点各基因型在两组间分布差异均无统计学意义（p值分别为：rs2227284，p=0.969; rs2243283, p=0.416; rs2243288p=0.685）。 2．统计分析显示IL-4基因rs2227284位点的T等位基因在病例组及对照组的频率分别为86.4%和87.2%；rs2227284位点的G等位基因在病例组及对照组的频率分别在分别为13.6%和12.8%。rs2243283位点的C等位基因在病例组及对照组的频率分别为79.8%和80.2%；rs2243283位点的G等位基因在病例组及对照组的频率分别为20.2%和19.8%。rs2243288位点的G等位基因在病例组及对照组的频率分别为80.8%和81.7%；rs2243288位点的A等位基因在病例组及对照组的频率分别为19.2%和18.3%。结论：经卡方检验，三个位点rs2227284、 rs2243283和rs2243288的等位基因频率在病例组与对照组间均无统计学差异（P值分别为rs2227284，P=0.655，OR(95%CI)=1.071(0.793-1.445)；rs2243283，P=0.849，，OR(95%CI)=0.976(0.758-1.257)； rs2243288， P=0.659，OR(95%CI)=1.060(0.818-1.375)）。 3．病例组与对照组间加性模型、显性模型和隐性模型三种不同的遗传模型也显示无统计学差异(rs2227284次要等位基因为G，加性模型、显性模型和隐性模型的p值分别为0.771，0.563，0.766；rs2243283次要等位基因为G，加性模型、显性模型和隐性模型的p值分别为0.571,0.599,0.071；rs2243288次要等位基因为A，加性模型、显性模型和隐性模型的p值分别为0.902,0.691,0.555)。 4．结果显示IL-4单体型频率GCA、TCA、TCG及TGG在病例组分别为13.5%、5.4%、60.9%、19.8%；对照组分别为12.8%、5.5%、62.0%、19.7%。分析显示无明显的统计学意义。P值分别为GCA，P=0.670；TCA,P=0.989；TCG，P=0.733；TGG，P=0.950。结论中国汉族人群中IL-4基因标签单核苷酸多态性(tag Single nucleotidepolymorphisms, tagSNPs) rs2227284，rs2243283和rs2243288可能与HBV感染的慢性化无关。
[Abstract]:BACKGROUND The consequences of hepatitis B virus (HBV) infection are mainly affected by virus, host and environment. With the increasing awareness of HBV, the influence of host genetic factors on the consequences of HBV infection has attracted more and more attention. Cytokine gene polymorphism has become a research hotspot. Interleukin-4 (IL-4) plays a key role in regulating the dynamic balance of T-lymphocyte subsets, and the imbalance of T-lymphocyte subsets can affect human response to therapeutic vaccines and susceptibility to human autoimmune diseases. Interferon-gamma (IFN-gamma) and inflammatory mediators are produced to prevent inflammation from damaging the liver. It has also been reported that mutations in the IL-4 gene may alter its expression and its downstream signals, thereby increasing individual susceptibility to immune-related liver diseases. Thus, its single nucleotide polymorphism (SNP) may be involved. It can be correlated with the incidence and clinical outcomes of chronic hepatitis B (CHB).
Objective To study the relationship between IL-4rs2227284G/T, rs2243283C/G and rs2243288A/G loci SNP and chronic HBV infection in Chinese Han population.
Methods 501 patients with chronic HBV were randomly divided into case group and 301 patients with acute self-limited HBV infection as control group. The linkage disequilibrium coefficients (D') between two or two loci of the above three loci were calculated.
Result
1. The distribution frequencies of TT, GT and GG genotypes at rs2227284 locus were 74.3%, 24.3% and 1.4% respectively in case group, 76.1%, 22.3% and 1.6% in control group, 33.1%, 63.3%, 3.6% in case group, 30.2%, 65.1%, 4.7% in control group, and 30.2%, 65.1%, GA, AA genotypes at rs2243288 locus, respectively. _2 test showed that there was no significant difference in the genotypes of the above three loci between the two groups (p value: rs2227284, P = 0.969; rs2243283, P = 0.416; rs2243288 P = 0.685).
2. Statistical analysis showed that the frequencies of T allele at rs2227284 locus of IL-4 gene were 86.4% and 87.2% respectively in case group and control group, the frequencies of G allele at rs2227284 locus were 13.6% and 12.8% respectively in case group and control group. The frequencies of C allele at rs2243283 locus were 79.8% and 8% respectively in case group and control group. The frequencies of G allele at rs2243283 locus were 20.2% and 19.8% in case group and control group, respectively. The frequencies of G allele at rs2243288 locus were 80.8% and 81.7% in case group and control group, and the frequencies of A allele at rs2243288 locus were 19.2% and 18.3% in case group and control group, respectively. The allele frequencies of rs2227284, rs2243283 and rs2243288 were not significantly different between the case group and the control group (P values were rs2227284, P = 0.655, OR (95% CI) = 1.071 (0.793-1.445), rs2243283, P = 0.849, OR (95% CI) = 0.976 (0.758-1.257), rs2243288, P = 0.659, OR (95% CI) = 1.060 (0.818) - 1.375).
3. There were no significant differences among the three genetic models of additive model, dominant model and recessive model between the case group and the control group (the P values of the secondary allele, additive model, dominant model and recessive model were 0.771, 0.563, 0.766 respectively; the secondary allele, additive model, dominant model and recessive model, rs2243283 were G, additive model, dominant model and recessive model, respectively). The P values of the model were 0.571, 0.599 and 0.071, and the secondary alleles of rs2243288 were A, additive model, dominant model and recessive model were 0.902, 0.691 and 0.555 respectively.
4. The results showed that the haplotype frequencies of IL-4 GCA, TCA, TCG and TGG were 13.5%, 5.4%, 60.9%, 19.8% in the case group, 12.8%, 5.5%, 62.0% and 19.7% in the control group, respectively.
Conclusion Tag Single nucleotide polymorphisms (tagSNPs) rs2227284, rs2243283 and rs2243288 may not be associated with the chronicity of HBV infection in Chinese Han population.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.6

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