一个非同义单核苷酸多态性基因HJURP相关的具有易感性肝癌中

StephenW

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        PLoS One. 2016 Feb 10;11(2):e0148618. doi: 10.1371/journal.pone.0148618.
A Non-Synonymous Single Nucleotide Polymorphism in the HJURP Gene Associated with Susceptibility to Hepatocellular Carcinoma among Chinese.Huang W1,2,3,4,5, Zhang H1,2,3, Hao Y1,2,3, Xu X6, Zhai Y1,2,3, Wang S7, Li Y7, Ma F8, Li Y1,2,3, Wang Z1,2,3, Zhang Y1,2,3, Zhang X1,2,3, Liang R9, Wei Z9, Cui Y4, Li Y4, Yu X10, Ji H6, He F1,2,3, Xie W4, Zhou G1,2,3.
Author information

• 1State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
• 2National Engineering Research Center for Protein Drugs, Beijing, China.
• 3National Center for Protein Sciences Beijing, Beijing, China.
• 4Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi, China.
• 5The Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
• 6Department of Gastroenterology and Hepatology, Jinling Hospital, Clinical School of Nanjing, Second Military Medical University, Nanjing, Jiangsu, China.
• 7Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, China.
• 8The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
• 9Liver Cancer Institute at Fusui County, Guangxi, China.
• 10Disease Prevention and Control Center at Haimen County, Jiangsu, China.
  

AbstractOBJECTIVE: HJURP (Holliday Junction-Recognizing Protein) plays dual roles in DNA repair and in accurate chromosome segregation during mitosis. We examined whether the single nucleotide polymorphisms (SNPs) of HJURP were associated with the risk of occurrence of hepatocellular carcinoma (HCC) among chronic hepatitis B virus (HBV) carriers from well-known high-risk regions for HCC in China.
METHODS: Twenty-four haplotype-tagging SNPs across HJURP were selected from HapMap data using the Haploview software. We genotyped these 24 SNPs using the using Sequenom's iPLEX assay in the Fusui population, consisting of 348 patients with HCC and 359 cancer-free controls, and further investigated the significantly associated SNP using the TaqMan assay in the Haimen population, consisting of 100 cases and 103 controls. The genetic associations with the risk of HCC were analyzed by logistic regression.
RESULTS: We observed an increased occurrence of HCC consistently associated with A/C or C/C genotypes of the non-synonymous SNP rs3771333 compared with the A/A genotype in both the Fusui and Haimen populations, with a pooled odds ratio 1.82 (95% confidence interval, 1.33-2.49; P = 1.9 × 10-4). Case-only analysis further indicated that carriers of the at-risk C allele were younger than those carrying the A/A genotype (P = 0.0016). In addition, the expression levels of HJURP in C allele carriers were lower than that in A/A genotype carriers (P = 0.0078 and 0.0010, for mRNA and protein levels, respectively).
CONCLUSION: Our findings suggest that rs3771333 in HJURP may play a role in mediating the susceptibility to HCC among Chinese.


PMID:26863619 [PubMed - as supplied by publisher]

StephenW

抽象
发给：
公共科学图书馆之一。 2016年2月10日; 11（2）：e0148618。 DOI：10.1371 / journal.pone.0148618。
一个非同义单核苷酸多态性基因HJURP相关的具有易感性肝癌中国人。
黄W1,2,3,4,5，张H1,2,3，郝Y1,2,3，徐X6，翟Y1,2,3，王S7，李Y7，马F8，李Y1,2,3王Z1,2,3，张Y1,2,3，张X1,2,3，R9亮，魏Z9，崔Y4，李Y4，俞X10，姬H6，他F1,2,3，谢W4，周G1,2,3。
蛋白质组学放射医学，北京，中国北京理工大学撰文信息国家重点实验室，北京蛋白质组研究中心。 2National工程技术研究中心蛋白质药物，北京，中国。 3National中心蛋白质科学北京，北京，中国。广西医科大学，广西南宁，中国附属肿瘤医院。广西医科大学，广西南宁，中国的5The第三附属医院。胃肠病学和肝病，金陵医院，南京临床学院，第二军医大学，南京，江苏，中国的6Department。实验病理学杂志7Department，放射医学，北京，中国北京理工大学。广西医科大学，广西南宁，中国的第八第一附属医院。 9Liver癌症研究所在扶绥县，广西，中国。 10Disease预防控制中心在海门县，江苏省，中国。
抽象
目的：
HJURP（霍利迪结认识蛋白）在DNA修复，并在有丝分裂过程中染色体的精确分离双重角色。我们检查是否HJURP的单核苷酸多态性（SNP）与慢性乙型肝炎病毒（HBV）携带者中肝细胞癌（HCC）在中国肝癌著名的高风险区域发生的风险有关。
方法：
跨HJURP二十四单倍型标签SNPs从使用Haploview软件HapMap计划数据进行选择。我们使用在扶绥人口使用Sequenom公司的IPLEX测定法中，由348 HCC患者和359无癌对照基因型这些24个SNP，并进一步研究了使用的TaqMan测定法中的海门人口显著相关联的SNP，由100例和103控制。与肝癌风险的遗传相关性采用Logistic回归分析。
结果：
我们观察到肝癌的增加的发生始终与A / C或在非同义SNP rs3771333的C / C基因型与A /同时在扶绥和海门市人口A基因型比较相关的，具有合并比值比1.82（95％区间，1.33-2.49; P = 1.9×10-4）。案例分析，只有进一步表示，在风险C等位基因的携带者比那些携带A / A基因型（P = 0.0016）年轻。此外，HJURP的C等位基因携带者的表达水平/ A基因型携带者（P = 0.0078和0.0010，为mRNA和蛋白水平，分别）均高于较低。
结论：
我们的研究结果表明，rs3771333在HJURP可以在调解中国人易患肝癌发挥作用。
结论：26863619 [考研 - 由出版商提供]