Is there a higher genetic load of susceptibility loci in familial ankylosing spondylitis?

Joshi, Reeti, Reveille, John D., Brown, Matthew A., Weisman, Michael H., Ward, Michael M., Gensler, Lianne S., Wordsworth, B. Paul, Evans, David M. and Assassi, Shervin (2012) Is there a higher genetic load of susceptibility loci in familial ankylosing spondylitis?. Arthritis Care and Research, 64 5: 780-784. doi:10.1002/acr.21601

Author Joshi, Reeti
Reveille, John D.
Brown, Matthew A.
Weisman, Michael H.
Ward, Michael M.
Gensler, Lianne S.
Wordsworth, B. Paul
Evans, David M.
Assassi, Shervin
Title Is there a higher genetic load of susceptibility loci in familial ankylosing spondylitis?
Journal name Arthritis Care and Research   Check publisher's open access policy
ISSN 2151-464X
Publication date 2012-05
Year available 2012
Sub-type Article (original research)
DOI 10.1002/acr.21601
Volume 64
Issue 5
Start page 780
End page 784
Total pages 5
Place of publication Hoboken, USA
Publisher John Wiley & Sons
Collection year 2013
Language eng
Formatted abstract
Several genetic risk variants for ankylosing spondylitis (AS) have been identified in genome-wide association studies. Our objective was to examine whether familial AS cases have a higher genetic load of these susceptibility variants.

Overall, 502 AS patients were examined, consisting of 312 patients who had first-degree relatives (FDRs) with AS (familial) and 190 patients who had no FDRs with AS or spondylarthritis (sporadic). All patients and affected FDRs fulfilled the modified New York criteria for AS. The patients were recruited from 2 US cohorts (the North American Spondylitis Consortium and the Prospective Study of Outcomes in Ankylosing Spondylitis) and from the UK-Oxford cohort. The frequencies of AS susceptibility loci in IL-23R, IL1R2, ANTXR2, ERAP-1, 2 intergenic regions on chromosomes 2p15 and 21q22, and HLA–B27 status as determined by the tag single-nucleotide polymorphism (SNP) rs4349859 were compared between familial and sporadic cases of AS. Association between SNPs and multiplex status was assessed by logistic regression controlling for sibship size.


HLA–B27 was significantly more prevalent in familial than sporadic cases of AS (odds ratio 4.44 [95% confidence interval 2.06, 9.55], P = 0.0001). Furthermore, the AS risk allele at chromosome 21q22 intergenic region showed a trend toward higher frequency in the multiplex cases (P = 0.08). The frequency of the other AS risk variants did not differ significantly between familial and sporadic cases, either individually or combined.

HLA–B27 is more prevalent in familial than sporadic cases of AS, demonstrating higher familial aggregation of AS in patients with HLA–B27 positivity. The frequency of the recently described non–major histocompatibility complex susceptibility loci is not markedly different between the sporadic and familial cases of AS.
Keyword Hla-B27
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
UQ Diamantina Institute Publications
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Created: Mon, 15 Apr 2013, 12:00:42 EST by Kylie Hengst on behalf of UQ Diamantina Institute