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

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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 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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • King Abdulaziz University
  • Skåne University Hospital
  • Fred Hutchinson Cancer Research Center
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Endokrinologi och diabetes
  • Pediatrik

Nyckelord

Originalspråkengelska
Sidor (från-till)44-51
Antal sidor8
TidskriftHLA: Immune Response Genetics
Volym97
Utgåva nummer1
Tidigt onlinedatum2020 okt 11
StatusPublished - 2021 jan
PublikationskategoriForskning
Peer review utfördJa