CD14/-159 and TNFα/-308 promoter polymorphisms are not associated with Development of Idiopathic Neonatal Hepatitis among Filipinos

Objective@# To determine if the CD14/-159 and the TNFα/-308 single nucleotide polymorphisms (SNPs) are associated with the development of Idiopathic Neonatal Hepatitis (INH) in Filipino children. @*Methods@#Genomic DNA from 33 patients diagnosed with INH and 33 age- and sex-matched controls, children without any liver disease, were recruited. Baseline serum total bilirubin (TB), direct bilirubin (DB), and alkaline phosphatase (ALP) of the patients were obtained from their medical records. Genotypes for CD14/159 and TNFα/-308 were determined via PCR and direct sequencing. @*Results@#No significant difference was seen between the frequency of the CD14/-159 T allele (p=0.86) nor the TNFα/-308 A allele (p=0.62) between INH patients and controls. There was also no significant difference between the genotypic distribution of the INH and control populations for both CD14/-159 (p=0.54) and TNFα/-308 (p=0.62). There were also no significant differences noted between the different genotypes of CD14/159 and TNFα/-308 and levels of alkaline phosphatase (p=0.65, p=0.91), total bilirubin (p=0.89, p=0.75), and direct bilirubin (p=0.93, p=0.68). @*Conclusion@#In this preliminary study, CD14/-159 and TNFα/-308 showed no association with the development of INH among Filipinos.

mRNA Expression Level of Interleukin Genes in the Determining Phases of Behcet's Disease

BACKGROUND: Behcet's disease (BD), first described in 1937 as a triadic complex of symptoms (oral aphthae, genital ulcers, and hypopyon uveitis), is a chronic, relapsing, multisystemic idiopathic inflammatory disease. OBJECTIVE: The objective of this study was to investigate the usability of messenger RNA (mRNA) expression of cytokine genes for following up patients with BD and also assess polymorphisms in these genes as to how they influence mRNA expression. METHODS: This study investigated the role of the IL1A -889(C/T), IL1B -511(C/T), and IL2 -330(T/G) polymorphisms by polymerase chain reaction (PCR)-restriction fragment length polymorphisms and the expression levels of the genes by real-time PCR in BD. RESULTS: The frequency of the IL2 -330 G allele was found to be significantly higher in patients with BD. A decreased level of IL1A gene expression was found in the patient group with clinically active BD compared to controls. Increased IL1B gene expression levels werefound in patient groups with active, inactive, or ocular BD (p<0.001). IL2 gene expression level manifested no significant change compared to controls in the patient group with clinically active BD; it increased in the groups with clinically inactive BD or ocular involvement. CONCLUSION: IL1A, IL1B, and IL2 gene expression, and IL2 promoter polymorphisms, may be valuable markers for predicting risk in the development of BD. We believe that the results reveal the importance of achieving a better understanding of BD and the prospects of developing future therapeutic strategies.

Correlation between the Promoter Polymorphism of Fibroblast Growth Factor 1 gene and Late-onset Alzheimer's Disease / 中国康复理论与实践

@#ObjectiveTo evaluate the correlation between the promoter polymorphism of Fibroblast Growth Factor 1 (FGF-1) and late-onset Alzheimer's disease (LOAD). MethodsClinic pathological data from 206 autopsies were analyzed, including 100 autopsy-confirmed LOAD patients and 106 age-matched non-demented controls. PCR-RFLP (Restriction fragment length polymorphism) approach was used to determine the genotype of the promoter polymorphism of FGF-1 gene. ResultsThe genotyping frequencies of the promoter polymorphism (-1385 A/G) were AA 20 (10%), GA 89 (43%), GG 97 (47%), respectively. There was significant (P=0.027) difference of genotyping frequencies between the cases and controls; GG genotype was positively associated with LOAD (odds ratio=2.02, 95%CI:1.16～3.52). ConclusionThe promoter polymorphism (-1385 A/G) of FGF-1 gene was associated with LOAD.

Promoter Polymorphism of RRM1 Gene in Korean Lung Cancer Population / 결핵및호흡기질환

BACKGROUND: LOH11A is a region with frequent allele loss (>75%) in lung cancer that is located on the centromeric part of chromosome 11p15.5. Clinical and cell biological studies suggest that this region contains a gene associated with metastatic tumor spread. RRM1 encoding the M1 subunit of ribonucleotide reductase, which is an enzyme that catalyses the rate-limiting step in deoxyribonucleotide synthesis, is located in the LOH11A region. METHODS: Polymorphisms were found at nucleotide position (-)37 (C/A) and (-)524 (C/T) from the beginning of exon 1 of the RRM1 gene that might regulate the expression of RRM1. We studied the polymorphisms in 127 Korean individuals (66 lung cancer and 61 normal controls) and compared with those of 140 American patients with lung cancer. RESULTS: CC, AC and AA were found at the (-)37 position in 64(50.4%), 55(43.3%), and 8(6.3%) out of 127 Korean individuals (66 cancer, 61 non-cancer patients), respectively. There was a similar frequency of allele A at (-)37 in the American(27.9%) and Korean population(28.0%). CC, CT and TT was found at the (-)524 position in 24(18.9%), 44(34.6%), and 59(46.5%) out of the 127 Korean individuals, respectively. There was a similar frequency of allele C at (-)524 in the American(34.6%) and Korean population(36.2%).There was no difference in the frequency of the (-)37 and (-)524 genotypes between the cancer and non-cancer group. However there was a significant correlation of the genotypes between (-)37 and (-)524 (p<0.001), which suggests the possible coordination of these polymorphisms in the regulation of the promoter activity of the RRM1 gene. CONCLUSION: RRM1 promoter polymorphisms were not found to be significant risk factors for lung cancer. However, a further study of the promoter activity and expression of the RRM1 gene according to the pattern of the polymorphism will be needed.

Tumor Necrosis Factor-alpha-308G/A Promoter Polymorphism is Associated with the Severity of Gastric Carcinomas

PURPOSE: The pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), is a central mediator of the immune response involved in a wide range of immuno-inflammatory and infectious diseases. There is increasing evidence that TNF-alpha may promote the development and spread of the cancer. Polymorphisms in the TNF-alpha promoter have been related to TNF-alpha production. Therefore, we investigated the potential association of TNF-alpha genotypes with gastric cancer in the Korean population. METHODS: The study included 66 patients with gastric adenoma, 75 patients with gastric carcinoma, and 551 healthy controls. The -308 and -238 polymorphisms in the TNF-alpha promoter were analyzed by PCR- restriction fragment length polymorphism (RFLP). Distributions of TNF-alpha promoter polymorphisms were compared between groups by chi2 test. P values smaller than 0.05 were considered to be significant. RESULTS: The proportion of individuals carrying the TNF-alpha -308A allele was higher in the carcinoma group compared to controls and adenomas, but the differences were not significant (P=0.124). However, the TNF-alpha -308A allele was significantly associated with advanced gastric carcinoma (P=0.026), serosa invasion (P=0.004), neural invasion (P= 0.021), and lymph node metastasis (P=0.005). On the other hand, the TNF-alpha -238G/A polymorphism was not associated with the development of gastric adenoma and carcinoma and the severity of gastric carcinoma. CONCLUSION: These results suggest that the TNF-alpha -308A allele is associated with the severity of gastric carcinoma in terms of invasion and metastasis in the Korean population. Therefore, TNF-alpha promoter polymorphism could be used as a predictive marker of the severity of gastric carcinoma.

Association of IL-10 Gene Polymorphism with Development of Atopy / 소아알레르기및호흡기학회지

PURPOSE: There has been accumulating evidence that interleukin-10 (IL-10) influences on the production of proinflammatory cytokines, regulating the development of atopic diseases. In this study, we tested the genetic association between IL-10 haplotype polymorphism and the development of atopy. METHODS: The frequency of three single nucleotide polymorphisms (SNPs) at positions- 1082 (A/G), -819 (C/T), -592 (A/C) and corresponding haplotypes in the promotor region of the IL-10 gene were analysed in 174 atopic and 130 non-atopic children using Taqman method. The data were assessed for correlations with the eosinophil count and total serum IgE concentration. RESULTS: Three haplotypes (ATA, ACC, GCC) were identified without any ambiguous phasing due to linkage disequilibrium among SNPs. The frequency of IL-10 haplotype ACC was higher in non-atopic children compared to atopic children. (P=0.04) The frequency of IL-10 haplotype ATA was higher in atopic children compared to non-atopic children, but a statistical significance was not found. (P=0.099) ATA/ATA and ATA/ACC accounted for 80 percent of six different genotypes. Although the frequency of ATA/ATA genotype was higher in atopic children, there was no statistical significance. Although medians of serum IgE level and total eosinophil count were higher among atopic children with ATA/ATA genotype than in atopic children with ATA/ACC, no statistical significance was found. CONCLUSION: These results suggest that IL-10 promotor polymorphism may be associated with a genetic risk factor for the development of atopy in Korean children.