Dataset Information

CTLA-4 +49 G/A, a functional T1D risk SNP, affects CTLA-4 level in Treg subsets and IA-2A positivity, but not beta-cell function.

ABSTRACT: To investigate whether CTLA-4 +49 G/A (rs231775), a tagSNP in Asian, is a functional T1D SNP, we genotyped this SNP with 1035 T1D patients and 2575 controls in Chinese Han population. And 1280 controls measured insulin release and sensitivity based on an oral glucose tolerance test; 283 newly diagnosed T1D patients assayed C-peptide level based on a mixed-meal tolerance test. 31 controls were analyzed for different T cell subsets by multi-color flow cytometry. Under additive model, we found that CTLA-4 +49 G/A was significantly associated with T1D (P = 2.82E-04, OR = 1.25, 95% CI: 1.12-1.41), which was further confirmed by meta-analysis (P = 1.19E-08, OR = 1.65, 95% CI: 1.38-1.96) in Chinese Han population. Although we did not find any association between this SNP and beta-cell function in either healthy individuals or newly diagnosed T1D patients, healthy individuals carrying GG/GA genotypes had lower CTLA-4 expression in naïve or activated CD4 Treg subsets (P = 0.0046 and 0.0317 respectively). A higher positive rate of IA-2A was observed among T1D patients with GG genotype compared with AA (OR = 0.51, 95% CI: 0.30-0.84, p = 0.008). Collectively, CTLA-4 +49 G/A reached a GWAS significant association with T1D risk in Chinese Han population, affects CTLA-4 expression in Treg subsets and subsequently humoral immunity in T1D patients.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6031668 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CTLA-4 +49 G/A, a functional T1D risk SNP, affects CTLA-4 level in Treg subsets and IA-2A positivity, but not beta-cell function.

Chen Yang Y Chen Shu S Gu Yong Y Feng Yingjie Y Shi Yun Y Fu Qi Q Wang Zhixiao Z Cai Yun Y Dai Hao H Zheng Shuai S Sun Min M Zhang Mei M Xu Xinyu X Chen Heng H Xu Kuanfeng K Yang Tao T

Scientific reports 20180704 1

To investigate whether CTLA-4 +49 G/A (rs231775), a tagSNP in Asian, is a functional T1D SNP, we genotyped this SNP with 1035 T1D patients and 2575 controls in Chinese Han population. And 1280 controls measured insulin release and sensitivity based on an oral glucose tolerance test; 283 newly diagnosed T1D patients assayed C-peptide level based on a mixed-meal tolerance test. 31 controls were analyzed for different T cell subsets by multi-color flow cytometry. Under additive model, we found that ...[more]

PMID: 29973665

Similar Datasets

Project 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.

Dataset Information

CTLA-4 +49 G/A, a functional T1D risk SNP, affects CTLA-4 level in Treg subsets and IA-2A positivity, but not beta-cell function.

Publications

CTLA-4 +49 G/A, a functional T1D risk SNP, affects CTLA-4 level in Treg subsets and IA-2A positivity, but not beta-cell function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets