No evidence of a significant role for CTLA-4 in multiple sclerosis

Abstract

Variation in the cytotoxic T-lymphocyt e -associated protein 4 (CTLA-4) gene plays a significant role in deter mi ning susceptibility to autoi m m u ne thyroid disease and type 1 diabetes. Its role in multiple sclerosis is more controversial. In order to explore this logical candidat e more thoroughly we genotyped 771 multiple sclerosis trio families from the United Kingdom for the 3'untra nslate d region variable num ber tande m repeat, the CT60 single nucleotide polymorp his m (SNP) and five haplotype -tagging SNPs. No individual mark er or comm o n haplotype showed evidence of association with disease. These data suggest that any effect of CTLA-4 on multi ple sclerosis susceptibility is likely to be very small.

Genetic analysis of the exon 1 position 49 CD152 dimorphism in multiple sclerosis

“…However further evidence to support the hypothesis that polymorphism at position 49 of CD152 is associated with susceptibility to MS was not demonstrated. These data are in accordance to the results found in parallel studies by other investigators on predominantly Caucasian samples of ancestry (Bagos et al, 2007;Kantarci et al, 2003;Roxburgh et al, 2006). The range of G allele frequencies in these studies were between 35-56.5 in both HC and MS patients.…”

“…More recent studies in MS patients have not demonstrated sufficient evidence to link a particular genotype of the position 49 dimorphism to MS (Bagos et al, 2007;Roxburgh et al, 2006). However, many of these studies were either small pilot studies or conducted in very homogenous populations such Japan or small Norwegian villages (Fukazawa et al, 1999;Chataway et al, 1998;Kuokkanen et al, 1997).…”

“…For example, most studies conducted in China or Japan (Fukazawa et al, 1999;Ihara et al, 2001) show a tendency to the AA genotype, while others conducted in Scandinavian countries appear to favor the GG genotype. Still others have demonstrated no correlation at all (Bagos et al, 2007;Fukazawa et al, 2005;Roxburgh et al, 2006). However, the presence of large-scale studies with heterogeneous populations is lacking with only two meta-analyses having been conducted (Bagos et al, 2007;Kantarci et al, 2003).…”

Genetics of primary progressive multiple sclerosis

“…The G 49 allele of CTLA-4 was associated with MS susceptibility in two Scandinavian casecontrol studies (Harbo et al, 1999;Ligers et al, 1999) as well as in Olmsted County (Kantarci et al, 2003), and may influence disease severity in Japanese MS (Fukazawa et al, 1999b). However, multiple other case-control studies found no association with MS susceptibility (Masterman et al, 2000;Rasmussen et al, 2001;Bocko et al, 2003;van Veen et al, 2003a;Bonetti et al, 2004;Teutsch et al, 2004;Fukazawa et al, 2005;Lorentzen et al, 2005;Roxburgh et al, 2006). A family-based study in Canadian MS also found no association (Dyment et al, 2004); however, familybased studies with replication in French and southern European MS found an association, especially in families carrying the HLA-DRB1*15 haplotype (Alizadeh et al, 2003).…”

Alternative splicing in multiple sclerosis and other autoimmune diseases

“…Yet, reports on the association of CTLA-4 with MS have been inconsistent. [32][33][34][35][36][37][38][39][40][41] However confusing the association of CTLA-4 with MS, it is worth considering this gene as a potential contributor to the disease.…”