TNF-α polymorphisms in multiple sclerosis: no association with −238 and −308 promoter alleles,but the microsatellite allele all is associated with the disease in French patients

Abstract

Tumor necrosis faaor-α (TNF-α), a proinflammatory cytokine, is believed to play an important role in multiple sclerosis (MS) pathogenesis. The objective of this study was to determine whether sequence variation in the TNF-α gene is associated with MS. Bi-allelic polymorphisms in the TNF-α promoter region (TNF-α −238 and −308) and microsatellite TNF-α were previously reported. We investigated these polymorphisms in 74 French patients with MS, compared with 75 controls. No significant differences regarding the TNF-α −238 and −308 polymorphisms were observed between MS patient and controls Allele frequency for the all allele is in very significant association (P < 0.0001) with MS, due in part to the assoiation of the all allele with the HLA-DRBI*15 allele in patients.

Keywords

multiple sclerosis (MS)tumor necrosis factor-α (TNF-α)TNF-α promoter polymorphisms −238 and −308 microsatellite TNF-α<HLA-DRBI*15 allele

Get full access to this article

View all access options for this article.

References

Olerup O , Hillert J. (1991) HLA class II-associated genetic susceptibility in multiple sclerosis: a critical evaluation . Tiss Ant 38: 1-15 .

Ebers GC , Sadovnick AD. (1994) The role of genetic factors in multiple sclerosis susceptibility . J Neuroimmunol 54: 1-17 .

Carrol MC et al. (1987) Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes . Proc Natl Acad Sci USA 84: 8535-8539 .

Hauser SL. (1995) Tumor necrosis factor: immunogenetics and disease . Ann Neurol 38: 702-704 .

Wilson AG et al. (1997) Effects of a polymorphism in the human tumor necrosis factor a promoter on transcriptional activation . Proc Natl Acad Sci USA 94: 3195-3199 .

Jacob CO et al. (1990) Heritable MHC-Class II associated differences in production of TNF-α: relevance to genetic predisposition of SLE . Proc Natl Acad Sci USA 87: 1233-1237 .

Zipp F etal. (1998) Genetic control of multiple sclerosis: increased production of lymphotoxin and TNF-a by HLA-DR2 + T-cells . Ann Neurol 38: 723-730 .

Nedospasov SA , Udalova IA , Krupash DV. (1991) DNA sequence polymorphism at the tumor necrosis factor (TNF) locus. Numerous TNF/lymphotoxin alleles tagged by two closely linked microsatellites in the upstream region of the lymphotoxin (TNF-β) gene . J Immunol 147: 1053-1059 .

Roth AP et al. (1994) Tumor necrosis polymorphisms in multiple sclerosis: no additional association indepen-dant of HLA . J Neuroimmunol 51: 93-99 .

10.

Garcia-Merino A et al. (1996) Tumor necrosis factor (TNF) microsatellite haplotypes in relation to extended haplotypes, susceptibility to diseases associated with the major histocompatibility complex and TNF secretion . Hum Immunol 50: 11-21 .

11.

D'Alfonso S , Richiardi PM. (1994) A polymorphic variation in a putative regulation box of the TNFα promoter region . Immunogenetics 30: 150-154 .

12.

Wilson AG , di Giovine FS , Blakemore AIF , Duff GW. (1992) Single base polymorphisms in the human Tumor Necrosis Factor alpha (TNFα) gene detectable by NcoI restriction of PCR product . Hum Mol Genet 1: 353-353 .

13.

Udalova IA et al. (1993) Highly informative typing of the human TNF locus using six adjacent polymorphic markers . Genomics 16: 180-186 .

14.

Poser CM , Paty DW , Scheinberg L. (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols . Ann Neurol 13: 227-231 .

15.

Lucotte G et al. (1998) Genetic susceptibility to multiple sclerosis carried by class II HLA alleles 15 and 4 . Sem Hôp Paris 74: 1285-1289 (in French).

16.

He B et al. (1995) Tumor necrosis factor α-308 alleles in multiple sclerosis and optic neuritis . J Neuroimmunol 63: 143-147 .

17.

Huizinga TWJ et al. (1997) TNF-α promoter polymorphisms, production and susceptibility to multiple sclerosis in different groups of patients . J Neuroimmunol 72: 149-153 .

18.

Wingechuk D et al. (1997) A population-based case-control study of the tumor necrosis factor alpha −308 polymorphism in multiple sclerosis . Neurology 49: 626-628 .

19.

Sandberg-Wollheim M , Ciusani E , Salmaggi A , Pociot F. (1995) An evaluation of tumor necrosis factor micro-satellites in genetic susceptibility to multiple sclerosis . Mult Scler 1: 181-185 .

20.

Kirk CW et al. (1997) Tumor necrosis factor micro-satellites show association with multiple sclerosis . J Neurol Sci 147: 21-25 .

21.

Hofman FM , Hinton DR , Johnson K , Merril JE. (1989) Tumour necrosis factor identified in multiple sclerosis brain . J Exp Med 170: 607-612 .

22.

Selmaj KW , Raine CS. (1988) Tumour necrosis factor mediates myelin and oligodendrocyte damage in vitro . Ann Neurol 23: 339-346 .

23.

Knight JC et al. (1999) A polymorphism that affects OCT- 1 binding to the TNF promoter region is associated with severe malaria . Nat Genet 22: 145-150 .