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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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- Alshiekh, Shehab (author)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,King Abdulaziz University,Skåne University Hospital
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- Maziarz, Marlena (author)
- Lund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,Skåne University Hospital
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- Geraghty, Daniel E. (author)
- Fred Hutchinson Cancer Research Center
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- (creator_code:org_t)
- 2020-11-09
- 2021
- English 8 s.
- In: HLA: Immune Response Genetics. - : Wiley. - 2059-2302. ; 97:1, s. 44-51
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
Keyword
- celiac disease
- children
- HLA
- next-generation sequencing
- type 1 diabetes
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- art (subject category)
- ref (subject category)
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