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Different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease

Artikel i vetenskaplig tidskrift
Författare S. Alshiekh
L. P. Zhao
A. Lernmark
D. E. Geraghty
Åsa Torinsson Naluai
D. Agardh
Publicerad i Hla
Volym 90
Nummer/häfte 2
Sidor 95-101
ISSN 2059-2302
Publiceringsår 2017
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Sidor 95-101
Språk en
Länkar dx.doi.org/10.1111/tan.13065
Ämnesord celiac disease, genetic risk, HLA, massively parallel sequencing, next generation sequencing, generation sequencing reveals, genetic risk, hla, association, heritability, twins, ngs, Cell Biology, Immunology, Pathology
Ämneskategorier Klinisk medicin

Sammanfattning

Celiac disease is associated with the HLA-DR3-DQA1*05:01-DQB1*02:01 and DR4-DQA1*03:01-DQB1*03:02 haplotypes. In addition, there are currently over 40 non-HLA loci associated with celiac disease. This study extends previous analyses on different HLA haplotypes in celiac disease using next generation targeted sequencing. Included were 143 patients with celiac disease and 135 non-celiac disease controls investigated at median 9.8 years (1.4-18.3 years). PCR-based amplification of HLA and sequencing with Illumina MiSeq technology were used for extended sequencing of the HLA class II haplotypes HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1, respectively. Odds ratios were computed marginally for every allele and haplotype as the ratio of allelic frequency in patients and controls as ratio of exposure rates (RR), when comparing a null reference with equal exposure rates in cases and controls. Among the extended HLA haplotypes, the strongest risk haplotype for celiac disease was shown for DRB3*01:01:02 in linkage with DQA1*05:01-DQB1*02:01 (RR = 6.34; P-value < .0001). In a subpopulation analysis, DRB3*01:01:02-DQA1*05:01-DQB1*02:01 remained the most significant in patients with Scandinavian ethnicity (RR = 4.63; P < .0001) whereas DRB1*07:01:01-DRB4*01:03:01-DQA1*02:01-DQB1*02:02:01 presented the highest risk of celiac disease among non-Scandinavians (RR = 7.94; P = .011). The data also revealed 2 distinct celiac disease risk DR3-DQA1*05:01-DQB*02:01 haplotypes distinguished by either the DRB3*01:01:02 or DRB3*02:02:01 alleles, indicating that different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease. The associated risk of celiac disease for DR3-DRB3*01:01:02-DQA1*05:01-DQB1*02:01 is predominant among patients of Scandinavian ethnicity.

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