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High Throughput, Absolute Determination of the Content of a Selected Protein at Tissue Levels Using Quantitative Dot Blot Analysis (QDB)

Lacking a convenient, quantitative, high throughput immunoblot method for absolute determination of the content of a specific protein at cellular and ...

Binzhou Medical University

Based on 540 hepatocellular carcinoma patients and 540 age- and gender-matched controls, we tested the hypothesis that high mobility group protein box1 (HMGB1) and the receptor for advanced glycation end products (RAGE) genes are two potential candidate susceptibility genes for hepatocellular carcinoma in a multicenter hospital-based case-control analysis. The genotypes of seven widely-studied polymorphisms were determined, and their distributions respected the Hardy-Weinberg equilibrium. The mutant alleles of two polymorphisms, rs1045411 in HMGB1 gene and rs2070600 in RAGE gene, had significantly higher frequencies in patients than in controls (P < 0.001), with the power to detect this significance of being over 99.9%. Moreover, the above two polymorphisms increased the risk of developing hepatocellular carcinoma significantly, particularly for rs2070600 under the additive (odds ratio [OR] = 1.77; 95% confidence interval [CI]: 1.34-2.32; P < 0.001) and dominant (OR = 1.75; 95% CI: 1.23-2.50; P = 0.002) models after adjusting for body mass index, smoking and drinking. Haplotype analysis showed that the T-C-T haplotype (rs1045411-rs2249825-rs1415125) in HMGB1 gene was associated with a 2.47-fold (95% CI: 1.41-4.34; P = 0.002) increased risk of hepatocellular carcinoma compared with the commonest C-C-T haplotype after adjustment. In RAGE gene, the T-T-A-G (rs1800625-rs1800624-rs2070600-rs184003) (adjusted OR; 95% CI; P: 1.75; 1.02-3.03; 0.045) and T-T-A-T (adjusted OR; 95% CI; P: 1.95; 1.01-3.76; 0.048) haplotypes were associated with a marginally increased risk of hepatocellular carcinoma compared with the commonest T-T-G-G haplotype. In summary, we identified two risk-associated polymorphisms (rs1045411 and rs2070600), and more importantly a joint impact of seven polymorphisms from the HMGB1/RAGE axis in susceptibility to hepatocellular carcinoma.

A multicenter matched case-control analysis on seven polymorphisms from HMGB1 and RAGE genes in predicting hepatocellular carcinoma risk.

This study purported to investigate the impact of interleukin-10 (IL-10) gene 4 polymorphisms (-1082G>A, -819T>C, -592A>C and 210T>C) on peripheral blood IL-10 variation and prostate cancer (PCa) risk, with a special consideration given to various origins of between-study heterogeneity. 2 researchers independently fulfilled literature retrieval, quality assessment and information collection. Sub-grouped analyses per ethnicity, continent, design type, control source, genotyping procedure, genotype validation, age-matched status, study sample size, quality score and controls' mean age were conducted, respectively. Total 17 unduplicated studies (patients/controls: 7561/8101) were assessable for PCa risk, and 4 unduplicated studies (1189 subjects) for peripheral blood IL-10 variation. Pooling all assessable studies identified a marginally significant association between the -1082A allele and increased PCa risk (odds ratio (OR)=1.10, 95% confidence interval [CI]: 1.00 to 1.21) (Heterogeneity I2=64.3%), and no significance was detected in sub-grouped analyses of this polymorphism. Contrastingly, the -592C allele was significantly associated with reduced PCa risk in both prospective (OR=0.85, 95% CI: 0.77 to 0.95) and population-based (OR=0.92, 95% CI: 0.84 to 1.00) studies (Heterogeneity I2=0.0% and 18.1%). Moreover, carriers of combined -592CA/CC genotypes had a significant higher level of peripheral blood IL-10 than the -592AA genotype carriers (weighted mean difference=0.45 and 0.54 mg/dL, 95% CI: 0.23 to 0.67 and 0.30 to 0.39). The above comparisons possessed a low probability of publication bias. In sum, our findings suggested that IL-10 gene -592A>C polymorphism may represent a promising candidate locus for the occurrence of PCa, and further signified a contributing role of this polymorphism in prostate carcinogenesis.

Xiaoying Qi

Medicine and Pharmacy Research Center

Binzhou Medical University

High Throughput, Absolute Determination of the Content of a Selected Protein at Tissue Levels Using Quantitative Dot Blot Analysis (QDB)

Xiaoying Qi

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Medicine and Pharmacy Research Center

Binzhou Medical University

High Throughput, Absolute Determination of the Content of a Selected Protein at Tissue Levels Using Quantitative Dot Blot Analysis (QDB)

Medicine and Pharmacy Research Center