CTLA4 in multiple sclerosis. Lack of genetic association in a European Caucasian population but evidence of interaction with HLA-DR2 among Shanghai Chinese.
In the present study we searched for an association between multiple sclerosis (MS) and the gene encoding the cytotoxic T lymphocyte antigen 4 (CTLA4). Our experimental approach involved amplification of DNA fragments of the promoter and exon 1 of this gene containing single nucleotide polymorphisms followed by treatment of the amplified fragments with restriction enzymes for allele determination. Included in the study were 84 MS patients and 125 healthy control subjects from a population of white Caucasians. We also examined 42 MS patients and 86 healthy control subjects of Shanghai Chinese origin. Significant differences in the distribution of genotypes or haplotypes of the CTLA4 gene were not observed between MS patients and control subjects in either of the two populations (P>0.05). Moreover, we were not able to confirm a previous finding of an association between relapsing-remitting MS and the heterozygous genotype A/G of CTLA4 exon 1. There was no evidence to suggest that interaction between HLA-DR2 and CTLA4 is involved in the development of MS among European Caucasians (P>0.05). Opposed to this, analysis of the Shanghai Chinese suggested presence of such interaction (P=0.02). Our results do not support the assumption that CTLA4 influences susceptibility to MS in European Caucasians. On the other hand, they raise the possibility that the development of MS in other ethnic groups involves interaction between CTLA4 and DR2.
Department of Life Sciences, Roskilde University, PO Box 260, DK-4000 Roskilde, Denmark. hbr@virgil.ruc.dk
H B
HB
Rasmussen
M A
MA
Kelly
D A
DA
Francis
J
J
Clausen
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005060:Europe; D005838:Genotype; D015802:HLA-DR2 Antigen / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D018796:Immunoconjugates; D016015:Logistic Models; D009103:Multiple Sclerosis / Q000235:genetics*; D044465:White People / Q000235:genetics*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D015802:HLA-DR2 Antigen; D018796:Immunoconjugates; D000069594:Abatacept