Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-28423-9
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [81670715, 81270897]
- Key Program of National Natural Science Foundation of China [81530026]
- National Key Project of Research and Development Plan [2016YFC1305000]
- Jiangsu Province Youth Medical talents Project [QNRC2016584]
- Jiangsu Province Key Science and Technology Development Project [BE2017753]
- Jiangsu Provincial Special Program of Medical Science [BL2012026]
- Natural Science Foundation of Jiangsu province [BK2012486]
- Jiangsu Government Scholarship for Overseas Studies [JS-2013-260]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
Ask authors/readers for more resources
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 na ve or activated CD4Treg 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available