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PLoS One. 2016 Feb 10;11(2):e0148618. doi: 10.1371/journal.pone.0148618. eCollection 2016.

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

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

Abstract

OBJECTIVE:

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
PMCID:
PMC4749235
DOI:
10.1371/journal.pone.0148618
[Indexed for MEDLINE]
Free PMC Article

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