Radiographic severity of knee osteoarthritis is conditional on interleukin 1 receptor antagonist gene variations.
BACKGROUND
A lack of biomarkers that identify patients at risk for severe osteoarthritis (OA) complicates development of disease-modifying OA drugs.


OBJECTIVE
To determine whether inflammatory genetic markers could stratify patients with knee OA into high and low risk for destructive disease.


METHODS
Genotype associations with knee OA severity were assessed in two Caucasian populations. Fifteen single nucleotide polymorphisms (SNPs) in six inflammatory genes were evaluated for association with radiographic severity and with synovial fluid mediators in a subset of the patients.


RESULTS
Interleukin 1 receptor antagonist (IL1RN) SNPs (rs419598, rs315952 and rs9005) predicted Kellgren-Lawrence scores independently in each population. One IL1RN haplotype was associated with lower odds of radiographic severity (OR=0.15; 95% CI 0.065 to 0.349; p<0.0001), greater joint space width and lower synovial fluid cytokine levels. Carriage of the IL1RN haplotype influenced the age relationship with severity.


CONCLUSIONS
IL1RN polymorphisms reproducibly contribute to disease severity in knee OA and may be useful biomarkers for patient selection in disease-modifying OA drug trials.
Attur
Mukundan
M
Division of Rheumatology, New York University Hospital for Joint Diseases, New York, NY 10003, USA.
Wang
Hwa-Ying
HY
Kraus
Virginia Byers
VB
Bukowski
Jack F
JF
Aziz
Nazneen
N
Krasnokutsky
Svetlana
S
Samuels
Jonathan
J
Greenberg
Jeffrey
J
McDaniel
Gary
G
Abramson
Steven B
SB
Kornman
Kenneth S
KS
D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics / Q000473:pathology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000737:chemistry
D005819:Genetic Markers; C507763:IL1RN protein, human; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein