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CRYAB-650 C>G (rs2234702) affects susceptibility to Type 1 diabetes and IAA-positivity in Swedish population

Sun, Chengjun ; Lernmark, Åke LU orcid ; Landin-Olsson, Mona LU ; Scherstén, Bengt LU ; Ivarsson, Sten-A LU ; Sjöblad, S. LU and Åman, J (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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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.
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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&gt;G (rs762550), -650 C&gt;G (rs2234702) and -249 C &gt; 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 &lt; 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 &lt; 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}},
}