CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden
BACKGROUND: 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) isofor...
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Umeå universitet, Medicinsk och klinisk genetik
2007
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ftumeauniv:oai:DiVA.org:umu-7751 2024-02-11T10:07:09+01:00 CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden Mayans, Sofia Lackovic, Kurt Nyholm, Caroline Lindgren, Petter Ruikka, Karin Eliasson, Mats Cilio, Corrado M Holmberg, Dan 2007 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-7751 https://doi.org/10.1186/1471-2350-8-3 eng eng Umeå universitet, Medicinsk och klinisk genetik Umeå universitet, Institutionen för klinisk mikrobiologi Umeå universitet, Medicin BMC Medical Genetics, 2007, 8, http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-7751 doi:10.1186/1471-2350-8-3 PMID 17280620 ISI:000244329100001 Scopus 2-s2.0-33847306066 info:eu-repo/semantics/openAccess CT60 Genotype Sandwich Immunoassay AITD Patient Mouth Swab CT60 Polymorphism Medical Genetics Medicinsk genetik Article in journal info:eu-repo/semantics/article text 2007 ftumeauniv https://doi.org/10.1186/1471-2350-8-3 2024-01-17T23:36:34Z BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. Article in Journal/Newspaper Northern Sweden Umeå University: Publications (DiVA) BMC Medical Genetics 8 1 |
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Open Polar |
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Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
CT60 Genotype Sandwich Immunoassay AITD Patient Mouth Swab CT60 Polymorphism Medical Genetics Medicinsk genetik |
spellingShingle |
CT60 Genotype Sandwich Immunoassay AITD Patient Mouth Swab CT60 Polymorphism Medical Genetics Medicinsk genetik Mayans, Sofia Lackovic, Kurt Nyholm, Caroline Lindgren, Petter Ruikka, Karin Eliasson, Mats Cilio, Corrado M Holmberg, Dan CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden |
topic_facet |
CT60 Genotype Sandwich Immunoassay AITD Patient Mouth Swab CT60 Polymorphism Medical Genetics Medicinsk genetik |
description |
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. |
format |
Article in Journal/Newspaper |
author |
Mayans, Sofia Lackovic, Kurt Nyholm, Caroline Lindgren, Petter Ruikka, Karin Eliasson, Mats Cilio, Corrado M Holmberg, Dan |
author_facet |
Mayans, Sofia Lackovic, Kurt Nyholm, Caroline Lindgren, Petter Ruikka, Karin Eliasson, Mats Cilio, Corrado M Holmberg, Dan |
author_sort |
Mayans, Sofia |
title |
CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden |
title_short |
CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden |
title_full |
CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden |
title_fullStr |
CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden |
title_full_unstemmed |
CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden |
title_sort |
ct60 genotype does not affect ctla-4 isoform expression despite association to t1d and aitd in northern sweden |
publisher |
Umeå universitet, Medicinsk och klinisk genetik |
publishDate |
2007 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-7751 https://doi.org/10.1186/1471-2350-8-3 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
BMC Medical Genetics, 2007, 8, http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-7751 doi:10.1186/1471-2350-8-3 PMID 17280620 ISI:000244329100001 Scopus 2-s2.0-33847306066 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1186/1471-2350-8-3 |
container_title |
BMC Medical Genetics |
container_volume |
8 |
container_issue |
1 |
_version_ |
1790605318589251584 |