Common interleukin-6 promoter variants associate with the more severe forms of distal interphalangeal osteoarthritis.
BACKGROUND
The objective of this study was to investigate the relationship of the IL-6 promoter variants G-597A, G-572C and G-174C (rs1800797, rs1800796 and rs1800795, respectively), which have been shown to affect both the transcription and secretion of IL-6, to symptomatic distal interphalangeal (DIP) osteoarthritis (OA).


METHODS
A total of 535 women aged 45 to 63 years were included. Radiographs of both hands were taken and each DIP joint was evaluated (grade 0 to 4) for the presence of OA. Information on symptoms (pain, tenderness) in each joint was collected by using a self-administered questionnaire. Symptomatic DIP OA was defined by the presence of both radiographic findings of grade 2 or more and symptoms in at least two DIP joints, and symmetrical DIP OA by the presence of radiographic findings of grade 2 or more in at least one symmetrical pair of DIP joints. Common polymorphic loci in the IL-6 gene were amplified and the promoter haplotypes were reconstructed from genotype data with the PHASE program. Logistic regression analysis was used to examine the association between the IL-6 genotypes/diplotypes and the DIP OA outcome.


RESULTS
The G alleles of two promoter single nucleotide polymorphisms (SNPs) G-597A and G-174C were more common among the subjects with symptomatic DIP OA than among those with no disease (P = 0.020 and 0.024, corrected for multiple testing). In addition, the carriage of at least one G allele in these positions increased the risk of disease (P = 0.006 and P = 0.008, respectively). Carrying a haplotype with the G allele in all three promoter SNPs increased the risk of symptomatic DIP OA more than fourfold (odds ratio (OR) 4.45, P = 0.001). Carriage of the G-G diplotype indicated an increased risk of both symmetrical DIP OA (OR 1.52, 95% confidence interval 1.01 to 2.28) and symptomatic DIP OA (OR 3.67, 95% confidence interval 1.50 to 9.00).


CONCLUSIONS
The present study showed that the presence of G alleles at common IL-6 polymorphic promoter loci was associated with the more severe DIP OA outcomes, symmetrical and symptomatic.
Kämäräinen
Olli-Pekka
OP
Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, 90220 Oulu, Finland. olli-pekka.kamarainen@oulu.fi
Solovieva
Svetlana
S
Vehmas
Tapio
T
Luoma
Katariina
K
Riihimäki
Hilkka
H
Ala-Kokko
Leena
L
Männikkö
Minna
M
Leino-Arjas
Päivi
P
D000483:Alleles; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006225:Hand; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index
D015850:Interleukin-6