TY - JOUR
T1 - Multiple sclerosis
T2 - The frequency of allelic forms of tumor necrosis factor and lymphotoxin-alpha
AU - Mycko, M.
AU - Kowalski, W.
AU - Kwinkowski, M.
AU - Buenafe, A. C.
AU - Szymanska, B.
AU - Tronczynska, E.
AU - Plucienniczak, A.
AU - Selmaj, K.
N1 - Funding Information:
This paper was supported by a KBN grant 4.PO5A.097.08 and the grant from the M. Curie-Sklodowska Fund MZ/HHS-96-247.
PY - 1998/4/15
Y1 - 1998/4/15
N2 - The cytokines LTa and TNF have been implicated as major mediators of tissue injury in multiple sclerosis (MS). In this study we have assessed the frequency of specific polymorphisms for these genes in MS (n = 53) and controls (n = 81) using a highly sensitive, two stage nested polymerase chain reaction (PCR), with the second stage using mutation-specific primers. Genomic DNA was extracted from blood cells and the results confirmed by direct dideoxy chain termination sequencing. The frequency of the - 308 G to A mutation in the TNF promoter region in normal controls was 15% and in MS was 24%. For LTa gene the exon 3 polymorphism allele A was detected in 36% of controls and 34% of the MS patients. In MS, the combined genotype TNF G + A and LTa C + C was present 6 times more frequently (12%) than in controls (2%), and patients with this genotype showed the highest EDSS scores. We found the TNF and LTa polymorphisms to occur independently from the HLA class II DR2 allele distribution in MS. Whilst the G - A polymorphism in TNF gene promoter has been studied previously in MS, with conflicting results, this is the first study that has addressed the exon 3 polymorphism in LTa in MS. The results indicate that this polymorphism is not linked with the higher genetic predisposition for MS, but that combined TNF G + A and LTa C + C genotype might contribute to development of the disease.
AB - The cytokines LTa and TNF have been implicated as major mediators of tissue injury in multiple sclerosis (MS). In this study we have assessed the frequency of specific polymorphisms for these genes in MS (n = 53) and controls (n = 81) using a highly sensitive, two stage nested polymerase chain reaction (PCR), with the second stage using mutation-specific primers. Genomic DNA was extracted from blood cells and the results confirmed by direct dideoxy chain termination sequencing. The frequency of the - 308 G to A mutation in the TNF promoter region in normal controls was 15% and in MS was 24%. For LTa gene the exon 3 polymorphism allele A was detected in 36% of controls and 34% of the MS patients. In MS, the combined genotype TNF G + A and LTa C + C was present 6 times more frequently (12%) than in controls (2%), and patients with this genotype showed the highest EDSS scores. We found the TNF and LTa polymorphisms to occur independently from the HLA class II DR2 allele distribution in MS. Whilst the G - A polymorphism in TNF gene promoter has been studied previously in MS, with conflicting results, this is the first study that has addressed the exon 3 polymorphism in LTa in MS. The results indicate that this polymorphism is not linked with the higher genetic predisposition for MS, but that combined TNF G + A and LTa C + C genotype might contribute to development of the disease.
KW - Genetic polymorphism
KW - Genetic susceptibility
KW - LTa
KW - MS
KW - TNF
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U2 - 10.1016/S0165-5728(97)00255-5
DO - 10.1016/S0165-5728(97)00255-5
M3 - Article
C2 - 9628463
AN - SCOPUS:0032522204
SN - 0165-5728
VL - 84
SP - 198
EP - 206
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 2
ER -