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

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.

• Authors: Wenfeng Huang, Hongxing Zhang, Yumin Hao, Xiaobing Xu, Yun Zhai, Shaoxia Wang, Yang Li, Fuchao Ma, Yuanfeng Li, Zhifu Wang, Yang Zhang, Xiumei Zhang, Renxiang Liang, Zhongliang Wei, Ying Cui, Yongqiang Li, Xinsen Yu, Hongzan Ji, Fuchu He, Weimin Xie, Gangqiao Zhou
• Journal: PloS one (PLoS One) Vol. 11 Issue 2 Pg. e0148618 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 26863619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• HJURP protein, human

Topics

• Alleles
• Asian People (genetics)
• Carcinoma, Hepatocellular (ethnology, genetics, virology)
• Case-Control Studies
• Comorbidity
• DNA-Binding Proteins (genetics, physiology)
• Ethnicity (genetics)
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• Haplotypes (genetics)
• Hepatitis B, Chronic (epidemiology)
• Humans
• Incidence
• Linkage Disequilibrium
• Liver Neoplasms (ethnology, genetics, virology)
• Polymorphism, Single Nucleotide