Background
Methods
Sample collection
Genotyping
Statistical analysis
Results
Clinical characteristics | RA (Mean ± SD) | Control (Mean ± SD) |
p
| JIA (Mean ± SD) | Control (Mean ± SD) |
p
|
---|---|---|---|---|---|---|
Sex ratio (Female/Male) | 3.63 (842/232) | 3.47 (1314/378) | 0.17 | 4.56 (178/39) | 4.72 (312/66) | 0.89 |
Age (years) | 41.7 ± 11.6 | 39.6 ± 13.2 | 0.75 | 6.3 ± 3.1 | 6.7 ± 2.5 | 0.75 |
Onset age, years | 49.5 ± 7.9 | – | – | 7.5 ± 4.9 | – | – |
Bone erosions n (%) | 421 (39.1%) | – | – | 46 (21.3%) | – | – |
Shared epitope | 467 (43.5%) | – | – | 79 (36.4%) | – | – |
DAS28 | 4.7 ± 1.3 | – | – | 3.4 ± 1.1 | – | – |
ESR (mm/h) (0–10 mm/h) | 33.2 ± 12.5 | 4.5 ± 2.2 | <0.001 | 34.5 ± 19.3 | 4.3 ± 2.4 | <0.001 |
CRP (mg/l) (0.8–8 mg/l) | 25.8 ± 12.2 | 4.9 ± 1.3 | <0.001 | 19.3 ± 37.5 | 3.77 ± 1.4 | <0.001 |
IgA mg/mL (0.71–3.35 mg/mL) | 12.2 ± 2.7 | 2.88 ± 1.4 | <0.001 | 10.2 ± 2.4 | 2.59 ± 1.7 | <0.001 |
IgG mg/mL (7.6–16.6 mg/mL) | 45.7 ± 5.4 | 10.3 ± 4.1 | <0.001 | 29.6 ± 5.1 | 9.7 ± 1.3 | <0.001 |
IgM mg/mL (0.48–2.12 mg/mL) | 6.6 ± 1.3 | 1.78 ± 2.1 | <0.001 | 5.4 ± 1.7 | 1.88 ± 1.02 | <0.001 |
RF+, % | 826 (76.9%) | 0 (0%) | 37 (16.9%) | 0 (0%) | ||
CCP+, % | 766 (71.3%) | 0 (0%) | 33 (15.4%) | 0 (0%) |
Single-locus association
RA | JIA | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
SNPs (MAF) | Region | Position | Case (freq.) | Control (freq.) |
P
|
P
a
adj
| OR [95%CI]b
| Case (freq.) | Control (freq.) |
P
|
P
a
adj
| OR [95%CI]b
|
rs10759932(C) | 5’UTR | 27786349 | 0.32 | 0.29 | 0.37 | – | 1.10 [0.89–1.34] | 0.26 | 0.26 | 0.86 | – | 1.03 [0.78–1.34] |
rs4986790 (G) | Exon 3 | 27796507 | 0.02 | 0.006 |
0.005
|
0.03
|
3.43 [1.39–8.45]
| 0.02 | 0.008 | 0.06 | – | 2.65 [0.93–7.49] |
rs4986791 (T) | Exon 3 | 27796807 | 0.05 | 0.04 | 0.03 | 0.18 | 1.75 [1.09–2.82] | 0.07 | 0.05 | 0.12 | – | 1.46 [0.90–2.37] |
rs41426344 (C) | 3’UTR | 27799138 | 0.21 | 0.13 |
<0.001
|
<0.001
|
2.24 [1.76–2.85]
| 0.25 | 0.14 |
<0.001
|
<0.001
|
2.05 [1.52–2.77]
|
rs11536889 (C) | 3’UTR | 27799336 | 0.22 | 0.19 | 0.07 | – | 1.24 [0.98–1.56] | 0.23 | 0.19 | 0.19 | – | 1.21 [0.91–1.61] |
rs7873784 (C) | 3’UTR | 27800141 | 0.15 | 0.12 | 0.03 | 0.18 | 1.35 [1.03–1.77] | 0.13 | 0.14 | 0.68 | – | 0.93 [0.66–1.31] |
SNPs | Genotype | Control no. | RA no. | OR [95%CI] |
p
a
|
p
b
adj
| Control no. | JIA no. | OR [95%CI] |
p
a
|
p
b
adj
|
---|---|---|---|---|---|---|---|---|---|---|---|
rs10759932 (C) | TT | 844 | 498 | 0.87 [0.74–1.01] | 0.07 | – | 204 | 125 | 1.16 [0.83–1.62] | 0.39 | – |
CT | 696 | 466 | 1.09 [0.94–1.28] | 0.24 | – | 151 | 73 | 0.76 [0.54–1.08] | 0.13 | – | |
CC | 143 | 108 | 1.21 [0.93–1.57] | 0.15 | – | 23 | 19 | 1.48 [0.79–2.79] | 0.22 | – | |
rs4986790 (G) | AA | 1671 | 1029 |
0.28 [0.17–0.49]
|
<0.001
|
<0.001
| 372 | 208 | 0.37 [0.13–1.06] | 0.06 | – |
GA | 21 | 45 |
3.47 [2.06–5.87]
|
<0.001
|
<0.001
| 6 | 9 | 2.68 [0.94–7.64] | 0.06 | – | |
GG | 0 | 0 | – | – | – | 0 | 0 | – | – | – | |
rs4986791 (T) | CC | 1590 | 986 | 0.72 [0.53–0.96] | 0. 03 | 0.09 | 399 | 186 | 0.58 [0.35–0.97] | 0.04 | 0.12 |
CT | 100 | 85 | 1.37 [1.01–1.84] | 0.04 | 0.12 | 39 | 30 | 1.65 [0.99–2.73] | 0.05 | – | |
TT | 2 | 3 | – | – | – | 0 | 1 | – | – | – | |
rs41426344 (C) | GG | 1287 | 615 |
0.42 [0.36–0.49]
|
<0.001
|
<0.001
| 280 | 127 |
0.49 [0.35–0.70]
|
<0.001
|
<0.001
|
GC | 369 | 378 |
1.94 [1.64–2.31]
|
<0.001
|
<0.001
| 91 | 72 | 1.57 [1.08–2.26] | 0.02 | 0.06 | |
CC | 36 | 81 |
3.75 [2.51–5.6]
|
<0.001
|
<0.001
| 7 | 18 |
4.79 [1.97–11.67]
|
0.0002
|
0.0006
| |
rs11536889 (C) | GG | 1113 | 647 |
0.79 [0.67–0.92]
|
0.003
|
0.009
| 242 | 133 | 0.89 [0.63–1.26] | 0.51 | – |
GC | 518 | 372 | 1.20 [1.02–1.41] | 0.03 | 0.09 | 125 | 70 | 0.96 [0.67–1.37] | 0.84 | – | |
CC | 60 | 54 | 1.44 [0.99–2.09] | 0.06 | – | 11 | 14 | 2.3 [1.02–5.16] | 0.04 | 0.12 | |
rs7873784 (C) | GG | 1308 | 790 | 0.81 [0.68–0.97] | 0.02 | 0.06 | 278 | 165 | 1.14 [0.78–1.68] | 0.50 | – |
GC | 358 | 268 | 1.24 [1.03–1.48] | 0.02 | 0.06 | 96 | 48 | 0.83 [0.56–1.23] | 0.37 | – | |
CC | 25 | 16 | 1.01 [0.54–1.89] | 1.00 | – | 4 | 4 | 1.76 [0.43–7.09] | – | – |
Haplotype analysis
NO. | haplotypea
| RA | OR [95CI%], P
b
| JIA | OR [95CI%], P
b
| ||
---|---|---|---|---|---|---|---|
Control (freq.) | Case (freq.) | Control (freq.) | Case (freq.) | ||||
H1 | T A C G G G | 0.47 | 0.43 | 1.03 [0.99–1.17],0.29 | 0.45 | 0.42 | 0.72 [0.52–1.01],0.06 |
H2 | T A C G G C | 0.06 | 0.12 | 1.07 [0.83–1.33],0.07 | 0.06 | 0.10 | 1.74 [0.95–3.21],0.07 |
H3 | T A C G C G | 0.11 | 0.09 | 0.54 [0.22–1.11],0.13 | 0.10 | 0.07 | 0.66 [0.36–1.23],0.19 |
H4 | T G T C C G | 0.02 | 0.08 |
1.13 [0.77–1.26],0.001
| 0.04 | 0.08 |
2.06 [1.01–4.21] 0.04
|
H5 | T A C C C C | 0.003 | 0.01 | 1.09 [0.76–1.45],0.06 | 0.003 | 0.006 | 1.75 [0.11–2.86],0.39 |
H6 | C A C G G G | 0.06 | 0.06 | 1.01 [0.99–1.03],0.89 | 0.04 | 0.06 | 1.54 [0.72–3.31],0.26 |
H7 | C A C G C G | 0.01 | 0.02 | 1.10 [0.98–1.24],0.57 | 0.02 | 0.02 | 0.87 [0.26–2.93],0.78 |
H8 | C A C G C C | 0.003 | 0.001 | 0.86 [0.63–1.05],0.69 | 0.002 | 0.003 | 1.74 [0.11–2.04],0.54 |
H9 | C A C C G G | 0.14 | 0.11 | 0.98 [0.97–0.99],0.07 | 0.15 | 0.11 | 0.70 [0.42–1.16],0.17 |
H10 | C G T C C G | 0.03 | 0.13 |
1.15 [1.02–1.56],0.001
| 0.03 | 0.07 |
2.47 [1.11–5.49],0.02
|
Allelic/Genotypic distribution of RF and anti-CCP in RA and JIA
SNPs | Allele/Genotypes | RA |
P
a
,OR [95%CI] | JIA |
P
a
,OR [95%CI] | RA |
P
a
,OR [95%CI] | JIA |
P
a
,OR [95%CI] | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
RF+ (freq.) | RF− (freq.) | RF+(freq.) | RF− (freq.) | Anti-CCP+(freq.) | Anti-CCP−(freq.) | Anti-CCP+(freq.) | Anti-CCP−(freq.) | ||||||
rs4986790 | G | 0.11 | 0.13 | 0.15 | 0.14 | 0.25 | 0.21 | 0.13 | 0.11 | ||||
A | 0.89 | 0.87 | 0.74,0.94 [0.65–1.36] | 0.85 | 0.86 | 0.82,1.07 [0.59–1.97] | 0.75 | 0.79 | 0.55,1.19 [0.66–2.15] | 0.87 | 0.89 | 0.84,1.26 [0.97–1.93] | |
GG | 0.0 | 0.0 | – | – | – | – | 0.0 | 0.0 | – | 0.0 | 0.0 | – | |
GA | 0.33 | 0.29 | 0.51,1.17 [0.73–1.86] | 0.31 | 0.30 | 0.84,1.06 [0.57–1.99] | 0.34 | 0.32 | 0.75,0.88 [0.42–1.86] | 0.29 | 0.27 | 0.64,1.22 [0.79–1.88] | |
AA | 0.67 | 0.71 | 0.92,0.98 [0.63–1.52] | 0.69 | 0.70 | 0.84,0.94 [0.50–1.76] | 0.66 | 0.68 | 0.84,0.93 [0.45–1.90] | 0.71 | 0.73 | 0.79,0.46 [0.22–0.97] | |
rs41426344 | C | 0.17 | 0.08 | 0.19 | 0.08 | 0.15 | 0.06 | 0.16 | 0.05 | ||||
G | 0.83 | 0.92 |
<.0001,2.33 [1.65–3..01]
| 0.82 | 0.92 |
0.02,2.91 [1.11–7.56]
| 0.85 | 0.94 |
0.008,2.79 [1.28–6.11]
| 0.84 | 0.95 |
0.02,2.78 [1.21–6.74]
| |
CC | 0.04 | 0.01 |
0.01,1.45 [0.48–4.26]
| 0.04 | 0.015 |
0.001,3.23 [0.39–26.79]
| 0.03 | 0.01 | –,2.34 [0.27–20.45] | 0.02 | 0.01 | –,2.45 [0.36–18.75] | |
CG | 0.30 | 0.13 |
<.0001,2.82 [1.90–4.19]
| 0.30 | 0.13 |
0.009,2.76 [1.26–6.05]
| 0.23 | 0.09 |
0.003,3.37 [1.48–9.43]
| 0.22 | 0.10 |
0.002,2.94 [1.39–8.25]
| |
GG | 0.66 | 0.86 |
<.0001,0.37 [0.25–0.53]
| 0.65 | 0.85 |
0.002,0.32 [0.15–0.69]
| 0.74 | 0.90 |
<.0001,0.21 [0.09–0.48]
| 0.76 | 0.89 |
<.0001,0.34 [0.11–0.85]
|