No evidence for association of CTLA-4 gene polymorphisms with the risk of developing multiple sclerosis: a meta-analysis.
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).
Bagos
Pantelis G
PG
Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens, Greece. pbagos@biol.uoa.gr
Karnaouri
Anthi C
AC
Nikolopoulos
Georgios K
GK
Hamodrakas
Stavros J
SJ
D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human