Shehab Alshiekh1,2, Daniel E Geraghty3, Daniel Agardh1. 1. Department of Clinical Sciences, Lund University, Malmö, Sweden. 2. Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. 3. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Abstract
OBJECTIVES: HLA-DQ2 and DQ8 contribute to the strongest risk haplotypes for type 1 diabetes (T1D) and celiac disease (CD). The variation in genetic risk association is likely linked to different HLA class II loci susceptibility, but association studies of HLA class I alleles are scarce. The aim was to investigate HLA class I A, B, and C alleles polymorphisms in children with only T1D, CD, and a subgroup with both T1D and CD (T1D w/CD). MATERIALS AND METHODS: HLA class I A, B, and C genes were genotyped using next-generation targeted sequencing. A conditional analysis was performed on 68 children with T1D, 219 children with CD and seven children with T1D w/CD enrolled from a birth cohort study at high genetic risk children from the South of Sweden. RESULTS: Among 1764 HLA class I allele variants, A*29:02:01 in T1D w/CD was associated with both T1D (OR = 21.42 [1.05, 1322.4], p = 0.0231) and CD (OR = 35 [2.36, 529.12], p = 0.0051) along with C*05:01:01 with both T1D (OR = 5.54 [1.06, 24.8], p = 0.02) and CD (OR = 6.84 [1.46, 26.01], p = 0.0077). No independent effects of HLA-B allele associations were observed in T1D w/CD. CONCLUSION: Although the distribution of HLA class I alleles differs between children with T1D and CD, the A*29:02:01 and C*05:01:01 alleles showed shared risk association of both diseases.
OBJECTIVES: HLA-DQ2 and DQ8 contribute to the strongest risk haplotypes for type 1 diabetes (T1D) and celiac disease (CD). The variation in genetic risk association is likely linked to different HLA class II loci susceptibility, but association studies of HLA class I alleles are scarce. The aim was to investigate HLA class I A, B, and C alleles polymorphisms in children with only T1D, CD, and a subgroup with both T1D and CD (T1D w/CD). MATERIALS AND METHODS: HLA class I A, B, and C genes were genotyped using next-generation targeted sequencing. A conditional analysis was performed on 68 children with T1D, 219 children with CD and seven children with T1D w/CD enrolled from a birth cohort study at high genetic risk children from the South of Sweden. RESULTS: Among 1764 HLA class I allele variants, A*29:02:01 in T1D w/CD was associated with both T1D (OR = 21.42 [1.05, 1322.4], p = 0.0231) and CD (OR = 35 [2.36, 529.12], p = 0.0051) along with C*05:01:01 with both T1D (OR = 5.54 [1.06, 24.8], p = 0.02) and CD (OR = 6.84 [1.46, 26.01], p = 0.0077). No independent effects of HLA-B allele associations were observed in T1D w/CD. CONCLUSION: Although the distribution of HLA class I alleles differs between children with T1D and CD, the A*29:02:01 and C*05:01:01 alleles showed shared risk association of both diseases.