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Association of Hypoxia-Inducible Factor-2 Alpha Gene Polymorphisms with the Risk of Hepatitis B Virus-Related Liver Disease in Guangxi Chinese: A Case-Control Study

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Journal PLoS One
Date 2016 Jul 8
PMID 27384772
Citations 5
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Abstract

Objective: Hypoxia-inducible factor-2 alpha (HIF-2a) plays a major role in the progression of disease, although the role of HIF-2α gene polymorphisms in hepatitis B virus (HBV)-related diseases remains elusive. The aim of this study is to determine whether HIF-2a rs13419896 and rs6715787 single-nucleotide polymorphisms (SNPs) are associated with susceptibility to chronic hepatitis B (CHB), liver cirrhosis (LC), or hepatocellular carcinoma (HCC).

Method: A case-control study of 107 patients with CHB, 83 patients with LC, 234 patients with HCC, and 224 healthy control subjects was carried out, and the HIF-2a rs13419896 and rs6715787 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: No significant differences were observed in the genotype or allele frequency of two HIF-2a SNPs between the cases and controls (all p>0.05). However, in subgroup analysis by gender, the HIF-2a rs13419896 GA and AA genotypes were significantly associated with a risk of CHB (odds ratio [OR] = 3.565, 95% confidence interval [CI] = 1.123-11.314, p = 0.031 and OR = 12.506, 95% CI = 1.329-117.716, p = 0.027) in females, and the A allele of rs13419896 was associated with a risk of CHB (OR = 2.624, 95% CI = 1.244-5.537, p = 0.011) and LC (OR = 2.351, 95% CI = 1.002-5.518, p = 0.050) in females. The rs6715787 CG genotype polymorphism may contribute to a reduced risk of LC in the Guangxi Zhuang Chinese population (OR = 0.152, 95% CI = 0.028-0.807, p = 0.027), as determined via subgroup analysis by ethnicity. Moreover, binary logistic regression analyses that were adjusted by drinking status indicated that the AA genotype of rs13419896 may contribute to an increased risk of LC in the non-alcohol-drinking population (OR = 3.124, 95% CI = 1.091-8.947, p = 0.034). In haplotype analysis, GG haplotype was significantly associated with a reduced risk of LC (OR = 0.601, 95% CI = 0.419-0.862, p = 0.005).

Conclusions: The HIF-2a rs13419896 polymorphism is associated with an increased risk of CHB and LC in the Guangxi Chinese population, especially in females and in the non-alcohol-drinking population, while the HIF-2a gene rs6715787 polymorphism is associated with a decreased risk of LC in the Guangxi Zhuang population.

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References
1.
Purdue M, Johansson M, Zelenika D, Toro J, Scelo G, Moore L . Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3. Nat Genet. 2010; 43(1):60-5. PMC: 3049257. DOI: 10.1038/ng.723. View

2.
Nizet V, Johnson R . Interdependence of hypoxic and innate immune responses. Nat Rev Immunol. 2009; 9(9):609-17. PMC: 4343208. DOI: 10.1038/nri2607. View

3.
Bhandari T, Nizet V . Hypoxia-Inducible Factor (HIF) as a Pharmacological Target for Prevention and Treatment of Infectious Diseases. Infect Dis Ther. 2014; 3(2):159-74. PMC: 4269623. DOI: 10.1007/s40121-014-0030-1. View

4.
Harkisoen S, Arends J, van Erpecum K, van den Hoek A, Hoepelman A . Hepatitis B viral load and risk of HBV-related liver disease: from East to West?. Ann Hepatol. 2012; 11(2):164-71. View

5.
Lu Y, Sui J, Liu Y, Li R, Ma L, Zhang X . Association between hypoxia-inducible factor-1α gene polymorphisms and risk of chronic hepatitis B and hepatitis B virus-related liver cirrhosis in a Chinese population: a retrospective case-control study. Gene. 2015; 564(1):96-100. DOI: 10.1016/j.gene.2015.03.053. View