Interleukin-10 promoter polymorphism in multiple sclerosis: association with disease progression.
Interleukin-10 (IL-10) is a potent anti-inflammatory and immunosuppressive cytokine that modulates disease expression in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). In previous studies, two dinucleotide repeat elements (microsatellites G and R) were identified, respectively located about 1.1 and 4.0 kb upstream of the IL-10 gene transcription initiation site. Several of their alleles were found to be associated with the level of IL-10 production. The aim of our study was to determine whether sequence variations in the IL-10 gene were associated with MS susceptibility and progression. To do so, we analyzed the distribution of IL-10.R and IL-10.G alleles and genotype polymorphisms in MS patients and healthy controls. We then correlated our findings with disease severity in MS patients using the progression index (PI). Patients were classified as experiencing mild (PI < 0.5) or severe (PI > 0.5) disease progression. Our results show no association between the IL-10.R microsatellite and MS, regardless of disease severity. However, IL-10.G microsatellite genotyping showed that IL-10.G9/9, G10/13, G11/13 and G13/14 were more frequently found in patients with mild disease progression (p = 0.005). We also found that in patients with severe disease progression, IL-10.G9/10, G9/11, G9/13 and G12/13 were over-represented (p = 0.002). Our study indicates that neither the IL-10.R or the IL-10.G alleles are associated with predisposition to MS. However, several IL-10.G genotypes might emerge as markers of disease progression.
Almeras
Lionel
L
Department of Immunology, EA 2686, CHU de Lille, France. immunologie@univ-lille2.fr
Meresse
Bertrand
B
Seze
Jérôme
J
De Lefranc
D
D
Dubucquoi
Sylvain
S
Fajardy
Isabelle
I
Vermersch
Patrick
P
Prin
Lionel
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012016:Reference Values
D017931:DNA Primers; D016753:Interleukin-10