Investigating the genetic association between ERAP1 and spondyloarthritis.
OBJECTIVE
A robust association between polymorphisms in the non-major histocompatibility complex gene ERAP1 and ankylosing spondylitis (AS) in several populations was recently identified. The aim of the current study was to determine the level of association of ERAP1 polymorphisms with spondyloarthritis (SpA) in French/Belgian populations with particular attention to genotype-phenotype correlations.


METHODS
We studied 734 independent SpA cases and 632 controls from two European cohorts. Five single-nucleotide polymorphisms (SNPs), rs27044, rs17482078, rs10050860, rs30187 and rs2287987 were genotyped, and case-control association analyses were carried using PLINK 1.07 software. Linkage disequilibrium and haplotypes were estimated with Haploview. Analysis was first carried out in SpA as a whole group, and then separately in AS and non-radiographic SpA (non-AS) patients.


RESULTS
Consistent with previous studies conducted in AS, rs30187 was the most significantly associated SNP with SpA (p=0.008 in the French, and p=6.46×10(-4) in the Belgian cohorts). In the combined cohorts, this SNP was associated with both AS and non-AS (P(combined)= 3.9×10(-5) and P(combined)= 0.005, respectively). A similar trend was observed with other SNPs. The rs17482078/rs10050860/rs30187-CCT haplotype was significantly associated with increased risk of SpA in both cohorts (P(combined)= 9.08×10(-4)), including AS and non-AS (P(combined)=6.16×10(-4) and P(combined)=0.049, respectively), whereas the -TTC haplotype was associated with reduced risk of SpA, including AS and non-AS (P(combined)=2.36×10(-7), P(combined)= 5.69×10(-6) and P(combined)= 2.13×10(-4), respectively).


CONCLUSIONS
This is the first study to show an association between several polymorphisms located in ERAP1 and SpA as a whole. Our findings demonstrate consistent association of the same SNPs and haplotypes with both AS and non-AS subtypes of SpA.
Rheumatology Division, Hôpital Ambroise Paré, 9 Avenue Charles de Gaulle, Boulogne 92100, France. maxime.breban@apr.aphp.fr
Amir
A
Kadi
Brigitte
B
Izac
Roula
R
Said-Nahal
Ariane
A
Leboime
Liesbet
L
Van Praet
Kurt
K
de Vlam
Dirk
D
Elewaut
Gilles
G
Chiocchia
Maxime
M
Breban
D000328:Adult; D000626:Aminopeptidases / Q000235:genetics*; D001530:Belgium / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005602:France / Q000453:epidemiology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D015796:HLA-B27 Antigen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D025241:Spondylarthritis / Q000453:epidemiology* / Q000235:genetics*; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
D015796:HLA-B27 Antigen; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C464841:ERAP1 protein, human