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No evidence for association of CTLA-4 gene polymorphisms with the risk of developing multiple sclerosis: a meta-analysis

Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 15701, Greece, pbagos{at}biol.uoa.gr

Anthi C Karnaouri

Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 15701, Greece

Georgios K Nikolopoulos

Hellenic Centre for Diseases Control and Prevention, 3rd September 54, Athens 10433, Greece

Stavros J Hamodrakas

Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 15701, Greece

We conducted a meta-analysis concerning the association of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms with the risk of developing multiple sclerosis (MS). We identified 18 eligible studies summarizing information about 3375 MS cases and 2930 healthy controls. Two polymorphisms were of interest: the exon 1 +49 A/G polymorphism (in 18 studies) and the promoter-318 C/T polymorphism (in 10 studies). Using random-effects methods we found no evidence for association of the various contrasts of genotypes (or allele frequencies) with the disease. There was significant between-studies heterogeneity that could not be explained by the ethnicity of the populations studied or by other summary measures (gender, disease course, latitude). The major finding of the meta-analysis, apart from the lack of an overall association, consists of detecting a significant time trend of the OR for the contrast of GA versus GG+AA genotypes of the exon 1 +49 A/G polymorphism. In particular, using cumulative meta-analysis we found that the large number of conflicting results on the subject was triggered by the early appearance of a highly significant published result (a study that indicated a significant association of the genotype with the disease).

Key Words: CTLA-4 • genetic epidemiology • meta-analysis • multiple sclerosis • polymorphism • random effects

Multiple Sclerosis, Vol. 13, No. 2, 156-168 (2007)
DOI: 10.1177/1352458507078059


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