Dataset Information

A Non-Synonymous Single Nucleotide Polymorphism in the HJURP Gene Associated with Susceptibility to Hepatocellular Carcinoma among Chinese.

ABSTRACT: 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.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.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).Our findings suggest that rs3771333 in HJURP may play a role in mediating the susceptibility to HCC among Chinese.

SUBMITTER: Huang W

PROVIDER: S-EPMC4749235 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A Non-Synonymous Single Nucleotide Polymorphism in the HJURP Gene Associated with Susceptibility to Hepatocellular Carcinoma among Chinese.

Huang Wenfeng W Zhang Hongxing H Hao Yumin Y Xu Xiaobing X Zhai Yun Y Wang Shaoxia S Li Yang Y Ma Fuchao F Li Yuanfeng Y Wang Zhifu Z Zhang Yang Y Zhang Xiumei X Liang Renxiang R Wei Zhongliang Z Cui Ying Y Li Yongqiang Y Yu Xinsen X Ji Hongzan H He Fuchu F Xie Weimin W Zhou Gangqiao G

PloS one 20160210 2

<h4>Objective</h4>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.<h4>Methods</h4>Twenty-four haplotype-tagging SNPs across HJURP were selected from HapMap data using t ...[more]

PMID: 26863619

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Project description:BACKGROUND: PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines. Loss of Shp2 promotes hepatocellular carcinoma (HCC), suggesting that PTPN11 functions as a tumor suppressor in HCC tumorgenesis. The aim of this study was to evaluate the effects of the short tandem repeat (STR) polymorphism (rs199618935) within 3'UTR of PTPN11 on HCC susceptibility in Chinese populations. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the associations in 400 patients from Jiangsu province of China, validating the findings in an additional 305 patients from Shanghai of China. Unconditional logistic regression was used to analyze the association between rs199618935 and HCC risk. Additional biochemical investigations and in-silico studies were used to evaluate the possible functional significance of this polymorphism. Logistic regression analysis showed that compared with individuals carrying shorter alleles (11 and 12 repeats), those subjects who carry longer alleles (13 and 14 repeats) had a significantly decreased risk of HCC [adjusted odds ratio (OR) = 0.63, 95% confidence interval (CI) ?= 0.53-0.76, P = 2.00 × 10(-7)], with the risk decreased even further in those carrying allele 15 and 16 (adjusted OR = 0.46, 95% CI = 0.34-0.62, P = 1.00 × 10(-7)). Biochemical investigations showed that longer alleles of rs199618935 conferred higher PTPN11 expression in vivo and in vitro. The altered luciferase activities in reporter gene system suggested that STR regulation of PTPN11 expression could be a transcriptional event. Finally, in-silico prediction revealed that different alleles of rs199618935 could alter the local structure of PTPN11 mRNA. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings suggested that the STR polymorphism within PTPN11 contributes to hepatocarcinogenesis, possibly by affecting PTPN11 expression through a structure-dependent mechanism. The replication of our studies and further functional studies are needed to validate our findings.

Dataset Information

A Non-Synonymous Single Nucleotide Polymorphism in the HJURP Gene Associated with Susceptibility to Hepatocellular Carcinoma among Chinese.

Publications

A Non-Synonymous Single Nucleotide Polymorphism in the HJURP Gene Associated with Susceptibility to Hepatocellular Carcinoma among Chinese.

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