Dataset Information

Association of Paraoxonase 1 Gene Polymorphisms With the Risk of Hepatitis B Virus-related Liver Diseases in a Guangxi Population: A Case-control Study.

ABSTRACT: Paraoxonase 1 (PON1), a liver-induced glycoprotein enzyme responsible for antioxidant defense against reactive oxygen species and anti-inflammatory, has been linked to various cancers. The objective of this study was to explore the association of PON1 rs662 and rs705382 with the risk of chronic hepatitis B (CHB), hepatitis B virus-related liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in patients living in the Guangxi region of southern China. The PON1 rs662 and rs705382 single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 99 CHB patients, 84 LC patients, 258 HCC patients, and 221 healthy controls.Significant associations with CHB risk were observed for the rs705382 SNP after adjusting for sex, age, ethnicity, smoking, alcohol consumption, and body mass index. When stratified by sex and age, this positive association was significantly strengthened among men and individuals over 40 years old. Moreover, a decreased risk of LC was associated with the rs705382 CG and the combined GG + CG genotypes among women, with borderline statistical significance. In haplotype analyses, the haplotype GA was associated with a 1.68-fold increase in the risk of HCC.Our results showed that the PON1 rs705382 SNP might be a risk factor for CHB in Guangxi populations.

SUBMITTER: Lao X

PROVIDER: S-EPMC4674207 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Association of Paraoxonase 1 Gene Polymorphisms With the Risk of Hepatitis B Virus-related Liver Diseases in a Guangxi Population: A Case-control Study.

Lao Xianjun X Wang Xiaogang X Liu Yanqiong Y Lu Yu Y Yang Dongmei D Liu Minyan M Zhang Xiaolian X Rong Chengzhi C Qin Xue X Li Shan S

Medicine 20151201 48

Paraoxonase 1 (PON1), a liver-induced glycoprotein enzyme responsible for antioxidant defense against reactive oxygen species and anti-inflammatory, has been linked to various cancers. The objective of this study was to explore the association of PON1 rs662 and rs705382 with the risk of chronic hepatitis B (CHB), hepatitis B virus-related liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in patients living in the Guangxi region of southern China. The PON1 rs662 and rs705382 single-nucleot ...[more]

PMID: 26632904

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Project description:Reactive oxygen species (ROS) play critical roles in hepatocarcinogenesis. The catalase (CAT) enzyme is involved in the repair of ROS. Therefore, we investigate the association between CAT gene polymorphisms and the risk of hepatocellular carcinoma (HCC). A total of 715 subjects were divided into 4 groups: 111 chronic hepatitis B (CHB) patients, 90 hepatitis B virus (HBV)-related liver cirrhosis (LC) patients, 266 HBV-HCC patients, and 248 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect CAT gene rs1001179, rs769217, and rs7943316 polymorphisms. Binary logistic regression analyses adjusting for sex, age, ethnicity, smoking and alcohol consumption, and body mass index suggested that subjects carrying the rs769217 T allele were at marginally increased risk of CHB, LC, and HCC, with adjusted odds ratios (ORs) of 1.51 (95% confidence interval [CI]?=?1.04-2.20, P?=?0.029), 1.48 (95% CI?=?1.03-2.14, P?=?0.035), and 1.51 (95% CI?=?1.14-1.98, P?=?0.004), respectively. Similarly, those individuals carrying the rs769217 TT genotype had a moderately increased risk of CHB, LC, and HCC, with adjusted ORs of 2.11 (95% CI?=?1.05-4.22, P?=?0.035), 2.00 (95% CI, 1.01-3.95, P?=?0.047), and 1.93 (95% CI?=?1.14-3.28, P?=?0.015), respectively. Moreover, subjects carrying the rs769217 CT genotype and at least 1 copy of the T allele (dominant model) were 1.78 times and 1.83 times more likely to develop HCC, respectively (OR?=?1.78, 95% CI?=?1.16-2.73, P?=?0.009 and OR?=?1.83, 95% CI?=?1.23-2.71, P?=?0.003). This association between CAT rs769217 T alleles and HCC risk is significantly strengthened among men, nonsmokers, nondrinkers, and among individuals <50 years of age. Furthermore, we found 1 high-risk haplotype GTA for CHB (OR?=?1.45, 95% CI?=?1.05-2.01) and 1 protective haplotype GCA for HCC risk (OR?=?0.67, 95% CI?=?0.52-0.87). We did not found any significant difference in CAT rs1001179 and rs7943316 polymorphisms between controls and cases. Our findings suggest that the CAT rs769217 T allele is associated with increased risk of CHB, HBV-LC, and HBV-HCC in Guangxi population.

Project description:Hypoxia-inducible factor-2 alpha (HIF-2a) plays a major role in the progression of disease, although the role of HIF-2? 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).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).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).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.

Project description:The functions of ghrelin (GHRL) include anti-inflammatory effects, reduction of the fibrogenic response, protection of liver tissue, and regulation of cell proliferation. Genetic variations in the GHRL gene may play an important role in the development of chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we investigated whether GHRL gene polymorphisms and its serum levels are associated with hepatitis B virus (HBV)-related diseases risk in a Chinese population.176 patients with CHB, 106 patients with HBV-related LC, 151 patients with HBV-related HCC, and 167 healthy controls were recruited in the study. Genotyping of GHRL rs26311, rs27647, rs696217, and rs34911341 polymorphisms were determined with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA).Binary logistic regression analyses adjusting for gender and age revealed that a significant increased risk of LC was found in the GHRL rs26311 GC genotype and combined GC+CC genotypes when compared with the GG genotype (GC vs. GG: OR = 1.671, 95% CI = 1.013-2.757, P = 0.044; GC+CC vs. GG: OR = 1.674, 95% CI = 1.040-2.696, P = 0.034). In subgroup analysis by gender, binary logistic regression analyses adjusting for age showed that the GHRL rs26311 C allele and combined GC+CC genotypes were associated with a significantly increased risk to LC in males (C vs. G OR = 1.416, 95% CI = 1.017-1.972, P = 0.040; GC+CC vs. GG: OR = 1.729, 95% CI = 1.019-2.933, P = 0.042). In addition, we found significant decreased serum GHRL levels in LC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26311 polymorphism with serum GHRL levels in LC patients.These observations suggest that the GHRL rs26311 polymorphism is associated with an increased risk to HBV-related LC, especially in men. We also found an inverse association of serum GHRL levels with LC.

Dataset Information

Association of Paraoxonase 1 Gene Polymorphisms With the Risk of Hepatitis B Virus-related Liver Diseases in a Guangxi Population: A Case-control Study.

Publications

Association of Paraoxonase 1 Gene Polymorphisms With the Risk of Hepatitis B Virus-related Liver Diseases in a Guangxi Population: A Case-control Study.

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