Session Information
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
Genome-wide association studies (GWAS)
and meta-GWAS studies have identified >50 single nucleotide-polymorphisms
(SNPs) that are associated with susceptibility to rheumatoid arthritis (RA). It
is, however, not known whether these susceptibility SNPs are also associated
with disease activity in early RA. The purpose of this study was to analyze for
associations between 49 susceptibility SNPs and disease activity including
radiographic damage in early untreated RA patients.
Methods:
315
patients with DMARD naïve RA and disease duration <6 months were included
from two randomized controlled trials (1,2), Table 1.
The two trials had similar inclusion and exclusion criteria, which resulted in similar
demographic and clinical characteristics and thus, the two cohorts were combined
in the analysis. We genotyped 49 SNPs previously associated with disease
susceptibility in two large meta-GWAS studies (3,4)
with the TaqMan OpenArray system, Table 2 shows rs-numbers. The genotype
associations with disease activity score of 28 joints (DAS28) and radiographic
damage (modified Total Sharp Score, mTSS) were
evaluated using linear regression analysis adjusted for age, sex, treatment,
anti-CCP status and smoking.
Results:
Baseline characteristics were similar in the two
cohorts, Table 1. Table 2 shows the linear regression analysis between the 49
SNPs and DAS28 and mTSS at baseline and after one
year. Three SNPs were associated with mTSS at both
baseline and year one (rs13315591 PXK,
rs26232 C5orf30, rs2793108 ZEB1) and neither with DAS28 at baseline
nor at year one. There were modest effects on radiographic damage judged by a
β ranging from 1.04 to 2.43, with PXK
having the strongest effect. In summary, we found 12 P values <0.05 in 8
SNPs, but none had a P value ≤0.001. Five associations were found with
DAS28 and 7 with mTSS. None of the 196 associations
tested were significant when using the Bonferoni’s or
Sidak’s adjustment for multiple testing (both
P=0.00026).
Conclusion:
We found
three out of 49 susceptibility SNPs to be associated with radiographic damage
in 315 early RA patients before and after one year’s treatment. No SNPs were
consistently associated with DAS28. The results should be interpreted with some
reservation due to the large number of associations investigated.
References:
(1) Hetland ML et al. Arthritis Rheum 2006, 54: 1401-1409.
(2) Horslev-Petersen K et al. Ann Rheum Dis 2014, 73: 654-661.
(3) Zhernakova A et al. PLoS Genet 2011, 7:
e1002004.
(4) Stahl EA et al. Nat Genet
2010, 42: 508-514.
|
Table 1. Patient characteristics of the two cohorts included
|
|||||
|
Baseline
|
Cohort 1 (n = 180) |
Cohort 2 (n = 135) |
P-value
|
||
|
Age |
55 |
(27–78) |
52 |
(26–71) |
0.11 |
|
Female sex, % |
66 |
65 |
0.91 |
||
|
Disease duration, days
|
84 |
(42–162) |
98 |
(48–175) |
<0.001 |
|
Rheumatoid factor positive, % |
72 |
68 |
0.54 |
||
|
Anti-CCP positive, % |
65 |
60 |
0.41 |
||
|
Tender joint count 28
|
11 |
(3–26) |
9 |
(2–22) |
0.07 |
|
Swollen joint count 28
|
8 |
(2–23) |
8 |
(2–20) |
0.41 |
|
Patient’s global assesment, mm
|
67 |
(13–98) |
50 |
(10–91) |
<0.001 |
|
CRP, mg/liter |
14 |
(1–132) |
20 |
(2–105) |
0.04 |
|
DAS28 |
5.6 |
(3.8-7.7) |
5.3 |
(3.2-7.1) |
0.02 |
|
HAQ |
1.1 |
(0.1-2.5)
|
1 |
(0–2.3) |
0.02 |
|
Erosive disease (mTSS≥1), %
|
75 |
61 |
0.005 |
||
|
mTSS |
2 |
(0-19) |
3 |
(0-20) |
0.93 |
|
Year one
|
|||||
|
CRP, mg/liter |
2 |
(0.5-19)
|
7 |
(0.7-33)
|
<0.001 |
|
DAS28 |
2.0 |
(1.7-4.3) |
2.0 |
(1.3-5.1) |
0.13 |
|
mTSS |
3 |
(0-19) |
3 |
(0-24) |
0.88 |
|
DmTSS (year 1 – baseline)
|
0 |
(-2-6) |
0 |
(0-6) |
0.76 |
|
Values are medians with 5-95% percentile values in parentheses, unless otherwise stated. Anti-CCP = anti-cyclic citrullinated peptide, DAS28 = disease activity score 28 joints, HAQ = Health Assessment Questionnaire. Fisher’s exact test and Mann–Whitney rank sum test were used when appropriate. Cohort 1 = OPERA(2), Cohort 2 = CIMESTRA(1)
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To cite this abstract in AMA style:
Ammitzbøll CG, Steffensen R, Bøgsted M, Nielsen KR, Ellingsen T, Lund Hetland M, Junker P, Pødenphant J, Østergaard M, Johansen J, Hørslev-Petersen K, Stengaard-Pedersen K. Associations Between 49 Susceptibility SNPs and Disease Activity Including Radiographic Damage in Early Untreated Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/associations-between-49-susceptibility-snps-and-disease-activity-including-radiographic-damage-in-early-untreated-rheumatoid-arthritis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/associations-between-49-susceptibility-snps-and-disease-activity-including-radiographic-damage-in-early-untreated-rheumatoid-arthritis/