ERAP1 association with ankylosing spondylitis is attributable to common genotypes rather than rare haplotype combinations

Roberts, Amity R., Appleton, Louise H., Cortes, Adrian, Vecellio, Matteo, Lau, Jonathan, Watts, Laura, Brown, Matthew A. and Wordsworth, Paul (2017) ERAP1 association with ankylosing spondylitis is attributable to common genotypes rather than rare haplotype combinations. Proceedings of the National Academy of Sciences of the United States of America, 114 3: 558-561. doi:10.1073/pnas.1618856114


Author Roberts, Amity R.
Appleton, Louise H.
Cortes, Adrian
Vecellio, Matteo
Lau, Jonathan
Watts, Laura
Brown, Matthew A.
Wordsworth, Paul
Title ERAP1 association with ankylosing spondylitis is attributable to common genotypes rather than rare haplotype combinations
Formatted title
ERAP1 association with ankylosing spondylitis is attributable to common genotypes rather than rare haplotype combinations
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 1091-6490
0027-8424
Publication date 2017-01-17
Year available 2016
Sub-type Article (original research)
DOI 10.1073/pnas.1618856114
Open Access Status Not yet assessed
Volume 114
Issue 3
Start page 558
End page 561
Total pages 4
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Collection year 2017
Language eng
Formatted abstract
We investigated the proposal that ankylosing spondylitis (AS) is associated with unusual ERAP1 genotypes. ERAP1 haplotypes were constructed for 213 AS cases and 46 rheumatoid arthritis controls using family data. Haplotypes were generated from five common ERAP1 single nucleotide polymorphisms (SNPs)—rs2287987 (M349V), rs30187 (K528R), rs10050860 (D575N), rs17482078 (R725Q), and rs27044 (Q730E). Haplotype frequencies were compared using Fisher’s exact test. ERAP1 haplotypes imputed from the International Genetics of AS Consortium (IGAS) Immunochip study were also studied. In the family study, we identified only four common ERAP1 haplotypes (“VRNQE,” “MKDRQ,” “MRDRE,” and “MKDRE”) in both AS cases and controls apart from two rare (<0.5%) previously unreported haplotypes. There were no examples of the unusual ERAP1 haplotype combination (“*001/*005”) previously reported by others in 53% of AS cases. As expected, K528-bearing haplotypes were increased in the AS family study (AS 43% vs. control 35%), due particularly to an increase in the MKDRQ haplotype (AS 35% vs. control 25%, P = 0.01). This trend was replicated in the imputed Immunochip data for the two K528-bearing haplotypes MKDRQ (AS 33% vs. controls 27%, P = 1.2 × 10–24) and MKDRE (AS 8% vs. controls 7%, P = 0.004). The ERAP1 association with AS is therefore predominantly attributable to common ERAP1 haplotypes and haplotype combinations.
Keyword Ankylosing spondylitis
ERAP1
Haplotypes
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
 
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