Advanced

High-resolution genotyping indicates that children with type 1 diabetes and celiac disease share three HLA class II loci in DRB3, DRB4 and DRB5 genes

Alshiekh, Shehab LU ; Maziarz, Marlena LU ; Geraghty, Daniel E. ; Larsson, Helena E. LU and Agardh, Daniel LU (2021) In HLA 97(1). p.44-51
Abstract

Type 1 diabetes (T1D) and celiac disease (CD) share common genetic loci, mainly within the human leukocyte antigen (HLA) class II complex. Extended genotyping of HLA class II alleles and their potential risk for developing both diseases remains to be studied. The present study compared extended HLA-class II gene polymorphisms in children with T1D, CD, and a subgroup diagnosed with both diseases (T1D w/CD). Next-generation targeted sequencing (NGTS) of HLA-DRB3, DRB4, DRB5, DRB1, DQA1, DQB1, DPA1, and DPB1 alleles from DNA collected from 68 T1D, 219 CD, and seven T1D w/CD patients were compared with 636 HLA-genotyped Swedish children from the general population selected as controls. In comparison to controls, the DRB4*01:03:01 allele... (More)

Type 1 diabetes (T1D) and celiac disease (CD) share common genetic loci, mainly within the human leukocyte antigen (HLA) class II complex. Extended genotyping of HLA class II alleles and their potential risk for developing both diseases remains to be studied. The present study compared extended HLA-class II gene polymorphisms in children with T1D, CD, and a subgroup diagnosed with both diseases (T1D w/CD). Next-generation targeted sequencing (NGTS) of HLA-DRB3, DRB4, DRB5, DRB1, DQA1, DQB1, DPA1, and DPB1 alleles from DNA collected from 68 T1D, 219 CD, and seven T1D w/CD patients were compared with 636 HLA-genotyped Swedish children from the general population selected as controls. In comparison to controls, the DRB4*01:03:01 allele occurred more frequently in T1D w/CD (odds ratio (OR) = 7.84; 95% confidence interval (95% CI) = (2.24, 34.5), P = 0.0002) and T1D (OR = 3.86; 95% CI, (2.69, 5.55), P = 1.07 × 10−14), respectively. The DRB3*01:01:02 allele occurred more frequently in CD as compared to controls (OR = 7.87; 95% CI, (6.17, 10.03), P = 4.24 × 10−71), but less frequently in T1D (OR = 2.59; 95% CI, (1.76, 3.81), P = 7.29 × 10−07) and T1D w/CD (OR = 0.87; 95% CI, (0.09, 3.96), P ≤ 0.999). The frequency of the DRB4*01:03:01-DRB1*04:01:01-DQA1*03:01:01-DQB1*03:02:01 (DR4-DQ8) haplotype was higher in T1D w/CD (OR = 12.88; 95% CI (4.35, 38.14) P = 3.75 × 10−9), and moderately higher in T1D (OR = 2.13; 95% CI (1.18, 3.83) P = 0.01) compared with controls, but comparable in CD (OR = 1.45; 95% CI (0.94, 2.21), P = 0.08) and controls. Children with T1D and CD are associated with DRB4*01:03:01, DRB3*01:01:02, and DRB3*02:02:01 of which DRB4*01:03:01 confers the strongest risk allele for developing T1D w/CD.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
celiac disease, children, HLA, next-generation sequencing, type 1 diabetes
in
HLA
volume
97
issue
1
pages
8 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:33043613
  • scopus:85096703934
ISSN
2059-2302
DOI
10.1111/tan.14105
language
English
LU publication?
yes
id
a4e8995e-6e0b-4f8d-bbe2-d0a6d39fbc9b
date added to LUP
2020-12-07 14:52:02
date last changed
2021-02-23 03:50:00
@article{a4e8995e-6e0b-4f8d-bbe2-d0a6d39fbc9b,
  abstract     = {<p>Type 1 diabetes (T1D) and celiac disease (CD) share common genetic loci, mainly within the human leukocyte antigen (HLA) class II complex. Extended genotyping of HLA class II alleles and their potential risk for developing both diseases remains to be studied. The present study compared extended HLA-class II gene polymorphisms in children with T1D, CD, and a subgroup diagnosed with both diseases (T1D w/CD). Next-generation targeted sequencing (NGTS) of HLA-DRB3, DRB4, DRB5, DRB1, DQA1, DQB1, DPA1, and DPB1 alleles from DNA collected from 68 T1D, 219 CD, and seven T1D w/CD patients were compared with 636 HLA-genotyped Swedish children from the general population selected as controls. In comparison to controls, the DRB4*01:03:01 allele occurred more frequently in T1D w/CD (odds ratio (OR) = 7.84; 95% confidence interval (95% CI) = (2.24, 34.5), P = 0.0002) and T1D (OR = 3.86; 95% CI, (2.69, 5.55), P = 1.07 × 10<sup>−14</sup>), respectively. The DRB3*01:01:02 allele occurred more frequently in CD as compared to controls (OR = 7.87; 95% CI, (6.17, 10.03), P = 4.24 × 10<sup>−71</sup>), but less frequently in T1D (OR = 2.59; 95% CI, (1.76, 3.81), P = 7.29 × 10<sup>−07</sup>) and T1D w/CD (OR = 0.87; 95% CI, (0.09, 3.96), P ≤ 0.999). The frequency of the DRB4*01:03:01-DRB1*04:01:01-DQA1*03:01:01-DQB1*03:02:01 (DR4-DQ8) haplotype was higher in T1D w/CD (OR = 12.88; 95% CI (4.35, 38.14) P = 3.75 × 10<sup>−9</sup>), and moderately higher in T1D (OR = 2.13; 95% CI (1.18, 3.83) P = 0.01) compared with controls, but comparable in CD (OR = 1.45; 95% CI (0.94, 2.21), P = 0.08) and controls. Children with T1D and CD are associated with DRB4*01:03:01, DRB3*01:01:02, and DRB3*02:02:01 of which DRB4*01:03:01 confers the strongest risk allele for developing T1D w/CD.</p>},
  author       = {Alshiekh, Shehab and Maziarz, Marlena and Geraghty, Daniel E. and Larsson, Helena E. and Agardh, Daniel},
  issn         = {2059-2302},
  language     = {eng},
  number       = {1},
  pages        = {44--51},
  publisher    = {Wiley-Blackwell},
  series       = {HLA},
  title        = {High-resolution genotyping indicates that children with type 1 diabetes and celiac disease share three HLA class II loci in DRB3, DRB4 and DRB5 genes},
  url          = {http://dx.doi.org/10.1111/tan.14105},
  doi          = {10.1111/tan.14105},
  volume       = {97},
  year         = {2021},
}