Multiple sclerosis: the frequency of allelic forms of tumor necrosis factor and lymphotoxin-alpha

Mycko, Marcin P.; Kowalski, Wojciech; Kwinkowski, M.; Buenafe, Abigail C.; Szymańska, Bożena; Tronczyńska, E.; Płucienniczak, Andrzej; Selmaj, Krzysztof

doi:10.1016/s0165-5728(97)00255-5

Cited by 80 publications

(45 citation statements)

References 42 publications

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“…The number of genetic studies on the association of TNF SNPs is already in double figures. A number of studies have found no HLA-independent association between TNF SNPs or microsatellites and MS, [45][46][47][48][49][50][51] childhood MS, 52 or the severity of MS. 53 While this might appear to indicate that the case for TNF SNPs and MS is closed, the highest number of patients included in any of these studies was 78. 53 Two slightly larger studies 54,55 also found no significant associations between the À308 SNP and MS.…”

Section: Multiple Sclerosismentioning

confidence: 99%

Is there a future for TNF promoter polymorphisms?

2004

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The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied À308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.

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Section: Multiple Sclerosismentioning

confidence: 99%

Is there a future for TNF promoter polymorphisms?

2004

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“…13,14 Other studies, however, were unable to confirm this effect on TNF-a synthesis. [15][16][17] Another TNF-a polymorphism is characterized by a G to A substitution at position À238 (TNF-a À238G4A). Huizinga et al 15 observed an increase in TNF-a production in LPS-stimulated whole-blood cell cultures among individuals carrying the TNF-a À238GG genotype, while in a study by Pociot et al 17 this genotype had no influence on TNF-a production.…”

Section: Introductionmentioning

confidence: 99%

TNF-α promoter polymorphisms and primary open-angle glaucoma

Mossböck

Weger

Moray

et al. 2005

Eye

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Purpose Primary open-angle glaucoma (POAG) is a multifactorial optic neuropathy with a strong hereditary component. Recent studies suggested a role for tumour necrosis factor-a (TNF-a) in the pathogenesis of POAG. The purpose of the present study was to investigate a hypothesized association between the TNF-a À308G4A and À238G4A gene polymorphisms and the presence of POAG in a Caucasian population. Methods The present case-control study comprised 114 unrelated patients with POAG and 228 healthy control subjects, matched for age and gender. Genotyping of the TNF-a À308G4A and À238G4A polymorphisms was performed using polymerase chain reaction. Results Allelic frequencies and genotype distributions of both the TNF-a À308G4A and À238G4A gene polymorphisms did not significantly differ between patients with POAG and control subjects. Presence of the TNF-a À308A-allele was associated with an odds ratio (OR) of 0.96 for POAG, whereas an OR of 0.52 was found among carriers of the TNF-a À238A-allele. Conclusion Our data suggest that none of the investigated TNF-a gene polymorphisms is a major risk factor among Caucasian patients with POAG.

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“…27,28,[30][31][32][33][34][35] On the other hand, there have been numerous studies, which have correlated specific SNPs to TNF and to LTA expression levels in groups of individuals and from cell lines, but with varying results. [36][37][38][39][40] It is understood that the production level phenotype of an individual cytokine can have a major impact on immune responsiveness, and an abundance of studies have linked specific SNPs to disease. 41,42 As examples, TNF and LTA expression levels and SNPs have been shown to correlate with an individual's susceptibility to, severity of and/or prognosis of diseases such as HIV, multiple sclerosis and cerebral malaria [43][44][45][46] and with prognosis or outcome of allograft transplantation and malignancies.…”

Section: Introductionmentioning

confidence: 99%

“…[58][59][60][61] Although there are a plethora of studies suggesting an association between TNF and LTA SNPs, expression level phenotypes, HLA and disease, there are as many studies that are in conflict or that find no correlation. 36,41,42,50,62,63 As these types of studies examine either individual SNP or a subset of the reported SNPs, the discrepent results are likely to be a result of the linked SNPs that were not examined. To our knowledge, no study to date has taken into account all of the SNPs at these loci when assessing the effects on expression or the linkage to disease and HLA.…”

Section: Introductionmentioning

confidence: 99%

Novel polymorphisms and the definition of promoter ‘alleles’ of the tumor necrosis factor and lymphotoxin α loci: inclusion in HLA haplotypes

2003

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Tumor necrosis factor (TNF) and lymphotoxin alpha (LTA) influence a variety of cellular responses and play a complex role in the immune response. Several single nucleotide polymorphisms (SNPs) have been reported in these major histocompatibility complex (MHC)-linked loci; however, a comprehensive examination of polymorphisms in the promoter regions of TNF and LTA has not been carried out and was undertaken here. Seven novel SNPs in LTA were identified by sequence analysis of 69 samples. Eight novel TNF alleles and 16 novel LTA alleles were designated. The TNF alleles clustered into two closely related groups, while the LTA alleles clustered into three distinct groups using phylogenetic and percentage difference analyses. A total of 52 unique TNF-LTA-HLA haplotypes are reported. There appear to be some associations between TNF/LTA alleles and HLA haplotypes, but not with specific HLA alleles. The majority of the SNPs appear to be randomly associated within and between the two loci except for the LTA SNPs at À293, þ 81 and þ 369. These observations may provide an explanation for the oftentimes contradictory results of studies associating individual cytokine gene SNPs with expression level phenotypes, HLA and disease.

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Multiple sclerosis: the frequency of allelic forms of tumor necrosis factor and lymphotoxin-alpha

Cited by 80 publications

References 42 publications

Is there a future for TNF promoter polymorphisms?

Is there a future for TNF promoter polymorphisms?

TNF-α promoter polymorphisms and primary open-angle glaucoma

Novel polymorphisms and the definition of promoter ‘alleles’ of the tumor necrosis factor and lymphotoxin α loci: inclusion in HLA haplotypes

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