Table 3

Acenocoumarol use interacts with MGP OA risk variants and VKORC1 haplotype groups, leading to increased risk of overall incidence/progression of osteoarthritis

Acenocoumarol useJoints*Incidence/ProgressionOR95% CIOR95% CIP value
NN (%)Adj.Adj.Adj.
MGP rs1800801 alleles
 Non-users MGP non-risk allele carriers (A/A)4332205 (4.7%)11
 Non-users MGP risk allele carriers (T/*)7211274 (3.8%)0.830.69 to 1.000.860.71 to 1.040.11
 Users MGP non-risk allele carriers (A/A)28626 (9.1%)2.111.37 to 3.242.011.29 to 3.132.0×10–03
 Users MGP risk allele carriers (T/*)49258 (11.8%)2.822.08 to 3.842.571.87 to 3.541.1×10–08
VKORC1 haplotype groups
 Non-users low VKORC1 group (AA)173575 (4.3%)11
 Non-users intermediate VKORC1 gGroup (AB)5525203 (3.7%)0.840.64 to 1.110.840.64 to 1.100.2
 Non-users high VKORC1 group (BB)4448201 (4.5%)1.050.80 to 1.371.040.79 to 1.360.8
 Users low VKORC1 group (AA)15216 (10.1%)2.61.48 to 4.592.311.28 to 4.175.3×10–03
 Users intermediate VKORC1 group (AB)31724 (7.6%)1.811.13 to 2.921.530.34 to 2.519.1×10–02
 Users high VKORC1 group (BB)30542 (13.8%)3.532.37 to 5.273.352.22 to 5.057.2×10–09
  • Overall progression of osteoarthritis (OA) in RSI and RSII within the follow-up time associated with acenocoumarol use effect MGP rs1800801 OA risk variant and VKORC1 expression/VKA dosage haplotypes. Model used is a GEE (generalised estimated equations) multivariate logistic regression model including acenocoumarol use adjusted (Adj.) for age, sex, BMI, smoking, time between baseline and follow-up visit, baseline OA severity in Kellgren-Lawrence score, joint modelled, femoral neck BMD, HDL/total cholesterol ratio, physical activity, education level, hypertension, diabetes mellitus and Rotterdam Study cohort. VKORC1 haplotype groups are based on the H haplotypes, see online supplemental table S1. For MGP risk variants and carriers, see Table 1. Progression: number of joints showing overall OA progression; T/*: MGP osteoarthritis risk variant carrier (T/A) or (T/T).

  • *Number of individual knee and hip joints included in the analysis.

  • BMD, bone mineral density ; BMI, body mass index.