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CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden.
BMC Med Genet. 2007 Feb 06; 8:3.BM

Abstract

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.

Authors+Show Affiliations

Medical and Clinical Genetics, Dept of Medical Biosciences, Umeå University SE-90185 Umeå, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17280620

Citation

Mayans, Sofia, et al. "CT60 Genotype Does Not Affect CTLA-4 Isoform Expression Despite Association to T1D and AITD in Northern Sweden." BMC Medical Genetics, vol. 8, 2007, p. 3.
Mayans S, Lackovic K, Nyholm C, et al. CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden. BMC Med Genet. 2007;8:3.
Mayans, S., Lackovic, K., Nyholm, C., Lindgren, P., Ruikka, K., Eliasson, M., Cilio, C. M., & Holmberg, D. (2007). CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden. BMC Medical Genetics, 8, 3.
Mayans S, et al. CT60 Genotype Does Not Affect CTLA-4 Isoform Expression Despite Association to T1D and AITD in Northern Sweden. BMC Med Genet. 2007 Feb 6;8:3. PubMed PMID: 17280620.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden. AU - Mayans,Sofia, AU - Lackovic,Kurt, AU - Nyholm,Caroline, AU - Lindgren,Petter, AU - Ruikka,Karin, AU - Eliasson,Mats, AU - Cilio,Corrado M, AU - Holmberg,Dan, Y1 - 2007/02/06/ PY - 2006/08/17/received PY - 2007/02/06/accepted PY - 2007/2/7/pubmed PY - 2007/2/27/medline PY - 2007/2/7/entrez SP - 3 EP - 3 JF - BMC medical genetics JO - BMC Med. Genet. VL - 8 N2 - 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. SN - 1471-2350 UR - https://www.unboundmedicine.com/medline/citation/17280620/CT60_genotype_does_not_affect_CTLA_4_isoform_expression_despite_association_to_T1D_and_AITD_in_northern_Sweden_ L2 - https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-8-3 DB - PRIME DP - Unbound Medicine ER -