CRYAB-650 C>G (rs2234702) affects susceptibility to Type 1 diabetes and IAA-positivity in Swedish population
(2012) In Human Immunology 73(7). p.759-766- Abstract
BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).
METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in... (More)
BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).
METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.
RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.
CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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- author
- Sun, Chengjun ; Lernmark, Åke LU ; Landin-Olsson, Mona LU ; Scherstén, Bengt LU ; Ivarsson, Sten-A LU ; Sjöblad, S. LU and Åman, J
- author collaboration
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adolescent, Adult, Autoantibodies/blood, Diabetes Mellitus, Type 1/diagnosis, Female, Gene Frequency, Genetic Association Studies, Genotype, Humans, Insulin/immunology, Male, Polymorphism, Single Nucleotide, Promoter Regions, Genetic/genetics, Sweden, Young Adult, alpha-Crystallin B Chain/genetics
- in
- Human Immunology
- volume
- 73
- issue
- 7
- pages
- 759 - 766
- publisher
- Elsevier
- external identifiers
-
- pmid:22537749
- scopus:84862314668
- ISSN
- 0198-8859
- DOI
- 10.1016/j.humimm.2012.04.004
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
- id
- 81cb759b-e100-4a1d-bb69-4fa1150ec0bb
- date added to LUP
- 2021-10-14 13:24:15
- date last changed
- 2024-06-01 18:29:38
@article{81cb759b-e100-4a1d-bb69-4fa1150ec0bb, abstract = {{<p>BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).</p><p>METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.</p><p>RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.</p><p>CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.</p>}}, author = {{Sun, Chengjun and Lernmark, Åke and Landin-Olsson, Mona and Scherstén, Bengt and Ivarsson, Sten-A and Sjöblad, S. and Åman, J}}, issn = {{0198-8859}}, keywords = {{Adolescent; Adult; Autoantibodies/blood; Diabetes Mellitus, Type 1/diagnosis; Female; Gene Frequency; Genetic Association Studies; Genotype; Humans; Insulin/immunology; Male; Polymorphism, Single Nucleotide; Promoter Regions, Genetic/genetics; Sweden; Young Adult; alpha-Crystallin B Chain/genetics}}, language = {{eng}}, number = {{7}}, pages = {{759--766}}, publisher = {{Elsevier}}, series = {{Human Immunology}}, title = {{CRYAB-650 C>G (rs2234702) affects susceptibility to Type 1 diabetes and IAA-positivity in Swedish population}}, url = {{http://dx.doi.org/10.1016/j.humimm.2012.04.004}}, doi = {{10.1016/j.humimm.2012.04.004}}, volume = {{73}}, year = {{2012}}, }