Combined effect of HLA-DRB1*1501 and interleukin-1 receptor antagonist gene allele 2 in susceptibility to relapsing/remitting multiple sclerosis.
Susceptibility to multiple sclerosis (MS) is associated with HLA-DRB1*1501. Many reports have suggested associations with other loci but these results remain unconfirmed. We studied the IL-1 receptor antagonist (IL-1ra) gene polymorphism and the HLA-DR and DQ allele frequencies by DNA-based methods in both the primary chronic progressive form (PP MS) and the relapsing/remitting form (R/R MS). The frequency of DRB1*1501 and IL-1ra allele 2 were significantly higher in R/R MS. Association was more marked in the female sex and in patients with benign forms of R/R MS. On the other hand DR4 subtypes carrying a Val at position 86 in the DR beta chain were increased in PP MS. The present study indicates that MS is genetically heterogeneous and shows a combined effect of HLA-DR and IL-1ra genes in susceptibility to the R/R form of the disease.
de la Concha
E G
EG
Department of Immunology, San Carlos University Hospital, Madrid, Spain.
Arroyo
R
R
Crusius
J B
JB
Campillo
J A
JA
Martin
C
C
Varela de Seijas
E
E
Peña
A S
AS
Clavería
L E
LE
Fernandez-Arquero
M
M
D000483:Alleles; D016022:Case-Control Studies; D018450:Disease Progression; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D011897:Random Allocation; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D012008:Recurrence; D012720:Severity of Illness Index; D012737:Sex Factors; D012795:Sialoglycoproteins / Q000235:genetics*; D013030:Spain / Q000453:epidemiology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins