The type 1 diabetes susceptibility gene SUMO4 at IDDM5 is not associated with susceptibility to rheumatoid arthritis or juvenile idiopathic arthritis.
OBJECTIVE
Linkage and association of rheumatoid arthritis (RA) and rheumatoid factor (RF)-negative juvenile idiopathic arthritis (JIA) has previously been demonstrated to the type 1 diabetes (T1D) locus, IDDM5, on chromosome 6q25. An association of a methionine-to-valine polymorphism (rs237025, 163A --> G, M55V) in the SUMO4 gene within IDDM5 has recently been described in T1D. The objective of this study was to test the hypothesis that SUMO4 is a general autoimmune susceptibility gene by investigating whether the SUMO4 polymorphism is associated with RA and/or JIA.


METHODS
The SUMO4 SNP was genotyped in 875 RA patients, 668 JIA patients and 484 healthy controls using a TaqMan allelic discrimination assay. Allele and genotype frequencies were compared between cases and controls using the chi2 test. Analyses were also carried out with RA patients stratified by gender, age at onset, RF status, the presence of erosive disease and shared epitope status, while JIA patients were stratified by their International League of Associations for Rheumatology (ILAR) subgroup.


RESULTS
No deviation from Hardy-Weinberg equilibrium was detected in either set of cases or controls. No association was observed between rs237025 and RA (chi2 = 0.17, P = 0.93), or with any RA subset. Similarly, there was no association between this SNP and JIA (chi2 = 0.21, P = 0.90), or with any ILAR subgroup.


CONCLUSIONS
The M55V substitution in the SUMO4 gene is not associated with susceptibility to RA or JIA in the UK population studied. However, other candidate genes mapping within IDDM5 remain to be investigated.
Gibbons
L J
LJ
Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester. M13 9PT, UK. lgibbons@fs1.ser.man.ac.uk
Thomson
W
W
Zeggini
E
E
Worthington
J
J
Barton
A
A
Eyre
S
S
Donn
R
R
Hinks
A
A
D000368:Aged; D000369:Aged, 80 and over; D001171:Arthritis, Juvenile / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics*
C489647:SUMO4 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins