Interleukin-4/interleukin-4 receptor gene polymorphisms in hand osteoarthritis.
OBJECTIVE
IL-13/IL-4/IL-4R system has strong chondroprotective activity. We investigated polymorphisms in these genes as potential hand osteoarthritis (OA) susceptibility loci by performing a case-control association study.


METHODS
Eighteen common single nucleotide polymorphisms (SNPs) (nine in IL-4R, five in IL-4 and four in IL-13) were genotyped in 403 patients (380 females) with hand OA and 322 healthy controls (308 females).


RESULTS
Two SNPs (rs1805013 and rs1805015), mapping to the IL-4R gene, were associated with P-values of 0.0116 and 0.0305 respectively in the whole sample. As far as the non-erosive hand OA group (n=159) is concerned, the significance level of association of SNP rs1805013 is increased. After correction for multiple testing (correction for the 54 tests) the significance was not retained. None of the IL-13 SNPs analyzed showed association with hand OA. Some of the analyzed SNP within the IL-4 gene showed significant association with hand OA only when considering subgroups of patients. With respect to the CMC1 OA group, two SNPs in IL-4 (rs2243250 and rs2243274) showed association with a P-value of 0.027 and 0.018 respectively. None of these associations remained after correction for multiple testing.


CONCLUSIONS
The present study shows a trend to an association between non-erosive hand OA in Caucasian population and a genetic variant in the coding region of IL-4R gene. Our results, in keeping with previous data on hip OA, confirm the suggestion that IL-4/IL-4R system plays a role in OA pathogenesis. Further confirmation studies on different populations are necessary.
Vargiolu
M
M
Unità di Genetica Medica, Policlinico Universitario S. Orsola-Malpighi, Bologna, Italy.
Silvestri
T
T
Bonora
E
E
Dolzani
P
P
Pulsatelli
L
L
Addimanda
O
O
Mancarella
L
L
Punzi
L
L
Fioravanti
A
A
Facchini
A
A
Romeo
G
G
Meliconi
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006225:Hand; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019948:Receptors, Interleukin-4 / Q000235:genetics*
D019948:Receptors, Interleukin-4; D015847:Interleukin-4