Our data suggest a lack of association between rs11614913, rs895819 and rs2910164 and colorectal cancer risk in the Central-European Caucasian population, a population with an extremely high incidence of sporadic colorectal cancer.

No abstract

Sarcoidosis is a granulomatous disorder showing a clear association with MHC (HLA) class I and class II genes. In order to investigate whether polymorphisms of nearby pro-inflammatory genes located within the MHC class III region may also contribute to susceptibility to sarcoidosis or to its clinical manifestation, tumour necrosis factor-alpha (TNF-alpha) and lymphotoxin-alpha (LT-alpha) genes were chosen for analysis in a case-control association study. In order to evaluate the findings on the TNF-alpha and LT-alpha genes in connection with the closely linked MHC class II region, 'classical' HLA-DRB1 locus was also investigated. Polymerase chain reaction-based methodologies were used in order to characterize two single-nucleotide polymorphisms (TNF-308*G/A and LTAlpha+252*A/G) and HLA-DRB1 allele groups in 114 Czech patients with pulmonary sarcoidosis and 425 healthy controls. LTA+252*G and HLA-DRB1*13 allele carriers were more frequent in patients, compared to those in controls. By contrast, HLA-DRB1*07 carriers were less frequent among sarcoidosis patients. The overrepresentation of TNF-308*A, LTAlpha+252*G and HLA-DRB1*03 allele carriers was found in a subgroup of sarcoidosis patients presenting with Lofgren's syndrome (LS) by comparison with the subgroup of patients without LS (NLS; phenotype frequency LS vs NLS: 68.8 vs 37.1% for TNF-308*A, 93.8 vs 66.3% for LTA+252*G and 68.8 vs 21.3% for DRB1*03). The data suggest that the LTAlpha and HLA-DRB1 genes themselves or a gene located nearby contributes to the susceptibility to sarcoidosis and that TNF-308*A, LTA+252*G and HLA-DRB1*03 alleles are associated (directly or via linkage with unknown causative locus) with LS as a specific manifestation of the disease.

Rheumatoid arthritis (RA) is a model of multigenic inflammatory disorder in which tumor necrosis factor-alpha (TNF-alpha) plays an important role. Genetic factors may be implicated in the susceptibility to disease initiation as well as in severity of disease course. Elevated levels of TNF-alpha in the plasma and synovial fluid from RA patients may be associated with polymorphisms in the promoter region of the TNF-alpha gene. The aim of this study was to elucidate putative association between the -308 G/A polymorphism in the promoter region of the TNF-alpha gene and susceptibility to onset and severity of RA. A total of 130 RA patients and a control group of 150 healthy subjects with similar age and sex distribution were available for the study. All patients fulfilled the American College of Rheumatology revised criteria for RA. RA patients had a disease duration of at least 2 years. Radiographs of both hands of all RA patients were scored with the Steinbrocker method. There were 15 patients of stage I (nonerosive form) of RA and 114 patients of stages II-IV (erosive form). To assess the RA patient's functional ability, the Health Assessment Questionnaire (HAQ) was used. The -308 G/A promoter polymorphism of the TNF-alpha gene was detected by polymerase chain reaction and restriction fragment length polymorphism analysis. No differences in genotype distribution and allelic frequences of -308 G/A TNF-alpha promoter polymorphism have been found between RA patients and the control group. Significant differences have been observed within the RA group divided according to the radiographic progression of disease based on the Steinbrocker radiographic score and functional ability (HAQ). These results suggest an association of the -308 G/A polymorphism of the TNF-alpha gene with the severity of RA.

Our data suggest that combined genotypes composed of the TNF-alpha and LT-alpha gene polymorphisms may influence the susceptibility to chronic periodontitis. We also showed that, comparing the two genes, the 1/1 genotype of the NcoI polymorphism in the first intron of the LT-alpha gene is a more informative marker and it may be one of the protective genetic factors against chronic periodontitis in our population.