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CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden

Sofia Mayans1, Kurt Lackovic1, Caroline Nyholm2, Petter Lindgren1, Karin Ruikka3, Mats Eliasson34, Corrado M Cilio2 and Dan Holmberg1*

Author Affiliations

1 Medical and Clinical Genetics, Dept. of Medical Biosciences, Umeå University SE-90185 Umeå, Sweden

2 Cellular Autoimmunity Unit, Dept. of Clinical Sciences, Malmö University Hospital, Lund University, SE-20502, Malmö, Sweden

3 Department of Medicine, Sunderby Hospital, SE-97180 Luleå, Sweden

4 Department of Public Health and Clinical Medicine, Umeå University SE-90185 Umeå, Sweden

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BMC Medical Genetics 2007, 8:3  doi:10.1186/1471-2350-8-3

Published: 6 February 2007



Polymorphisms in and around the CTLA-4 gene have previously been associated to T1D and AITD in several populations. One such single nucleotide polymorphism (SNP), CT60, has been reported to affect the expression level ratio of the soluble (sCTLA-4) to full length CTLA-4 (flCTLA-4) isoforms. The aims of our study were to replicate the association previously published by Ueda et al. of polymorphisms in the CTLA-4 region to T1D and AITD and to determine whether the CT60 polymorphism affects the expression level ratio of sCTLA-4/flCTLA-4 in our population.


Three SNPs were genotyped in 253 cases (104 AITD cases and 149 T1D cases) and 865 ethnically matched controls. Blood from 23 healthy individuals was used to quantify mRNA expression of CTLA-4 isoforms in CD4+ cells using real-time PCR. Serum from 102 cases and 59 healthy individuals was used to determine the level of sCTLA-4 protein.


Here we show association of the MH30, CT60 and JO31 polymorphisms to T1D and AITD in northern Sweden. We also observed a higher frequency of the CT60 disease susceptible allele in our controls compared to the British, Italian and Dutch populations, which might contribute to the high frequency of T1D in Sweden. In contrast to previously published findings, however, we were unable to find differences in the sCTLA-4/flCTLA-4 expression ratio based on the CT60 genotype in 23 healthy volunteers, also from northern Sweden. Analysis of sCTLA-4 protein levels in serum showed no correlation between sCTLA-4 protein levels and disease status or CT60 genotype.


Association was found between T1D/AITD and all three polymorphisms investigated. However, in contrast to previous investigations, sCTLA-4 RNA and protein expression levels did not differ based on CT60 genotype. Our results do not rule out the CT60 SNP as an important polymorphism in the development of T1D or AITD, but suggest that further investigations are necessary to elucidate the effect of the CTLA-4 region on the development of T1D and AITD.