贵州医科大学学报

2015, v.40;No.177(06) 571-575+587

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宿主免疫系统IL-2、TNF-α基因启动子多态性与丙型肝炎病毒慢性感染的相关性研究
Correlation Study among Host Immune System IL-2,TNF-α Gene Promoter Polymorphisms and HCV Chronic Infection

许秀雯;李莹;童绍勇;姚宇峰;俞建昆;史荔;孙明波;
XU Xiuwen;LI Ying;TONG Shaoyong;YAO Yufeng;YU Jiankun;SHI Li;SUN Mingbo;Yunnan Province Key Laboratory of Severe Infectious Disease Vaccine Research and Development,China Medical Institute & Peking Union Medical College;

摘要(Abstract):

目的:探讨白细胞介素2(IL-2)以及肿瘤坏死因子-α(TNF-α)基因启动子SNP位点与丙型肝炎病毒(HCV)慢性感染的相关性。方法:选择云南地区汉族人群HCV慢性感染患者380例,健康体检人群367例,采用Taq Man探针基因分型方法对IL-2基因启动子SNPrs2069762、rs2069763和rs4833248,以及TNF-α基因启动子SNPrs1800629、rs3093668和rs3093726进行基因分型,并构建单倍型,统计IL-2和TNF-α多态性位点的等位基因频率与基因型频率、单倍型频率,分析SNPs及单倍型与HCV慢性感染的相关性。结果:IL-2基因启动子中,病例组和对照组相比,SNPrs2069762基因型差异有统计学意义(P<0.05,OR=0.864,95%CI为0.700~1.066),病例组CC基因型频率高于对照组(P<0.05),rs2069763等位基因差异具有统计学意义(P<0.05,OR=1.234,95%CI为1.007~1.513),病例组等位基因G频率高于对照组(P<0.05),rs4833248基因型和等位基因频率差异无统计学意义(P>0.05),rs2069762/rs2069763/rs4833248单倍型ATG差异有统计学意义(P<0.05,OR=0.812,95%CI为0.662~0.996),病例组单倍型ATG频率低于对照组(P<0.05);TNF-α基因启动子SNPrs1800629、rs3093668和rs3093726基因型、等位基因型和单倍型频率,在病例组和对照组中差异无统计学意义(P>0.05)。结论:在云南汉族群体中,IL-2基因启动子SNPrs2069762 CC基因型和rs2069763 G等位基因可能是HCV慢性感染的易感因素,rs2069762/rs2069763/rs4833248单倍型ATG可能是HCV慢性感染的保护性因素;TNF-α基因启动子SNPrs1800629、rs3093668和rs3093726与HCV慢性感染没有相关性。
Objective: To investigate the correlation among HCV chronic infection and SNPs in IL-2and TNF-α gene promoter. Method: A total of 380 patients with HCV chronic infection and 367 Healthy controls of Yunnan Han people were selected. Taq Man probe genotyping was applied to detect the IL-2 gene promoter SNP rs2069762,rs2069763 and rs4833248,coupled with TNF-α gene promoter SNP rs1800629,rs3093668,rs3093726,then constructing haplotype. Estimating allele frequency and genotype frequency,and haplotype frequency of IL-2 and TNF-αSNP. Then analyzing correlation between SNPs and haplotype AGT and HCV chronic infection. Results: Concerning IL-2 gene promoter of infection group and control group,SNP rs2069762 genotypic variation showed significant difference( P < 0. 05,OR = 0. 864,95% CI: 0. 700 ~ 1. 066),and allele frequency of genotype CC in HCV chronic infection patients was higher than that of control group( P < 0. 05); the rs2069763 allele showed a significant difference( P < 0. 05,OR = 1. 234,95% CI1. 007 ~ 1. 513) and the allele G frequency of infection group was higher than that of control group( P < 0. 05); the genotype and allele frequency of rs4833248 displayed no significant difference( P > 0. 05); rs2069762 / rs2069763 /rs4833248 haplotype ATG showed significant difference( P < 0. 05,OR = 0. 812,95% CI: 0. 662 ~0. 996) and haplotype ATG frequency of infection group was lower than control group( P < 0. 05).Genotype,allele and haplotype frequency of rs1800629,rs3093668,rs3093726 in TNF-α had no statistical significance in both groups( P > 0. 05). Conclusions: For Han people in Yunnan province,the rs2069762 genotype CC and rs2069763 allele G in IL-2 are potential predisposing factors of HCV chronic infection. rs2069762 / rs2069763 / rs4833248 haplotype ATG might play a protective role in HCV chronic infection. SNP rs1800629,rs3093668,rs3093726 in TNF-α gene promoter show no correlation with HCV chronic infection.

关键词(KeyWords): 云南;肝炎病毒,丙型;感染;单核苷酸多态性;白细胞介素2;肿瘤坏死因子α
Yunnan;hepatitis C virus;infection;single nucleotide polymorphism;interlukin-2;tumor necrosis factor-α

Abstract:

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基金项目(Foundation): 国家自然科学基金资助项目(81160197);; 吴阶平医学基金项目(300.6750.13395)

作者(Author): 许秀雯;李莹;童绍勇;姚宇峰;俞建昆;史荔;孙明波;
XU Xiuwen;LI Ying;TONG Shaoyong;YAO Yufeng;YU Jiankun;SHI Li;SUN Mingbo;Yunnan Province Key Laboratory of Severe Infectious Disease Vaccine Research and Development,China Medical Institute & Peking Union Medical College;

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DOI: 10.19367/j.cnki.1000-2707.2015.06.006

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