Background
Methods
Study population, ethics and exclusion criteria
DNA extraction and genotyping of the CARD8 C10X (rs2043211) polymorphism
Olink proteomics
Other variables
Statistics
Results
Genotype distribution in the CARD8 gene
Additive model
| ||||
Total
|
TT
|
TA
|
AA
| |
n
|
n
(%)
|
n
(%)
|
n
(%)
| |
Men | 233 | 101 (43) | 105 (45) | 27 (12) |
NEU women | 383 | 176 (46) | 174 (45) | 33 (9) |
EU women | 128 | 69 (54) | 51 (40) | 8 (6) |
Total
| 744 | 346 (47) | 330 (44) | 68 (9) |
Dominant model
| ||||
Total
|
TT
|
TA + AA
| ||
n
|
n
(%)
|
n
(%)
| ||
Men | 233 | 101 (43) | 132 (57) | |
NEU women | 383 | 176 (46) | 207 (54) | |
EU women | 128 | 69 (54) | 59 (46) | |
Total
| 744 | 346 (47) | 398 (53) | |
Recessive model
| ||||
Total
|
TT + TA
|
AA
| ||
n
|
n
(%)
|
n
(%)
| ||
Men | 233 | 206 (88) | 27 (12) | |
NEU women | 383 | 350 (91) | 33 (9) | |
EU women | 128 | 120 (94) | 8 (6) | |
Total
| 744 | 676 (91) | 68 (9) |
Basic characteristics of the LBA cohort based on genotypes in the rs2043211 polymorphism in the CARD8 gene
Total
|
TT
|
TA
|
AA
| |
---|---|---|---|---|
Men (
n
= 233)
a
| ||||
Age (years) | 22.0 (2.0) | 21.9 (2.0) | 22.0 (2.1) | 22.8 (1.6) |
Height (cm) | 181.7 (6.7) | 181.6 (6.3) | 181.5 (7.1) | 182.4 (7.0) |
Weight (kg) | 77.7 (11.5) | 77.0 (10.7) | 78.1 (12.8) | 79.2 (9.0) |
BMI (kg/m2) | 23.5 (3.1) | 23.3 (3.0) | 23.7 (3.4) | 23.8 (2.4) |
LDL (mmol/L) | 2.3 (0.7) | 2.2 (0.6) | 2.4 (0.8) | 2.5 (0.6) |
Triglycerides (mmol/L) | 0.8 (0.4) | 0.8 (0.3) | 0.8 (0.4) | 0.9 (0.3) |
Systolic blood pressure (mm Hg) | 124.9 (11.9) | 123.9 (12.5) | 126.2 (11.9) | 123.5 (9.5) |
Insulin (mU/L) | 6.8 (4.9, 9.1) | 6.8 (5.0, 9.4) | 7.0 (4.9, 9.1) | 6.7 (4.3, 8.8) |
CRP (mg/L) | 0.5 (0.3, 1.1) | 0.4 (0.3, 1.0) | 0.6 (0.2, 1.5) | 0.6 (0.2, 1.0) |
Non-estrogen using women (
n
= 383)
a
| ||||
Age (years) | 21.9 (2.0) | 22.1 (1.9) | 21.7 (2.0) | 21.8 (2.0) |
Height (cm) | 168.6 (6.6) | 168.3 (6.1) | 168.9 (7.1) | 168.8 (6.3) |
Weight (kg) | 63.7 (11.1) | 64.2 (10.5) | 63.1 (11.8) | 63.9 (11.0) |
BMI (kg/m2) | 22.4 (3.5) | 22.6 (3.4) | 22.1 (3.5) | 22.4 (3.7) |
LDL (mmol/L) | 2.2 (0.6) | 2.2 (0.7) | 2.2 (0.6) | 2.2 (0.6) |
Triglycerides (mmol/L) | 0.7 (0.3) | 0.7 (0.3) | 0.7 (0.3) | 0.9 (0.5) |
Systolic blood pressure (mm Hg) | 109.8 (8.8) | 110.3 (9.1) | 109.2 (8.2) | 110.5 (10.1) |
Insulin (mU/L) | 7.0 (5.1, 9.8) | 7.0 (5.1, 9.7) | 6.8 (5.1, 9.6) | 8.4 (6.7, 10.5) |
CRP (mg/L) | 0.6 (0.3, 1.1) | 0.5 (0.3, 1.1) | 0.5 (0.3, 1.0) | 0.7 (0.4, 1.1) |
Estrogen-using women (
n
= 128)
a
| ||||
Age (years) | 21.7 (1.8) | 21.7 (1.8) | 21.8 (1.9) | 21.6 (1.4) |
Height (cm) | 168.6 (5.8) | 168.0 (6.2) | 169.5 (5.3) | 168.0 (5.6) |
Weight (kg) | 63.2 (10.6) | 62.3 (8.5) | 64.8 (13.3) | 60.3 (5.5) |
BMI (kg/m2) | 22.2 (3.1) | 22.0 (2.5) | 22.5 (3.9) | 21.4 (1.8) |
LDL (mmol/L) | 2.6 (0.8) | 2.6 (0.9) | 2.5 (0.7) | 3.1 (0.9) |
Triglycerides (mmol/L) | 1.0 (0.4) | 1.0 (0.4) | 1.0 (0.4) | 1.0 (0.6) |
Systolic blood pressure (mm Hg) | 112.8 (8.9) | 112.1 (8.6) | 114.2 (9.1) | 109.6 (9.8) |
Insulin (mU/L) | 7.1 (4.9, 10.1) | 6.8 (4.4, 10.1) | 7.0 (5.6, 9.9) | 9.0 (7.5, 10.3) |
CRP (mg/L) | 1.6 (0.7, 3.1) | 1.9 (0.9, 3.1) | 1.0 (0.6, 3.0) | 2.3 (0.5, 3.9) |
Association between rs2043211 genotype in the CARD8 gene and inflammatory proteins in the LBA cohort
Additive model
Men | NEU women | EU Women | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Model 1a
| Model 2b
| Model 1a
| Model 2b
| Model 1a
| Model 2b
| ||||||||||
Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| ||||
ADA | 0.008 | 0.926 | 0.005 | 0.956 | -0.017 | 0.793 | -0.012 | 0.856 | 0.047 | 0.696 | 0.038 | 0.760 | |||
AXL | 0.105 | 0.118 | 0.106 | 0.117 | -0.091 | 0.069 | -0.085 | 0.095 | -0.004 | 0.968 | 0.004 | 0.969 | |||
CCL20 | -0.361 | 0.023 | -0.353 | 0.030 | 0.128 | 0.311 | 0.080 | 0.538 | 0.174 | 0.451 | 0.162 | 0.495 | |||
CD40 | -0.177 | 0.027 | -0.139 | 0.084 | -0.080 | 0.271 | -0.098 | 0.183 | 0.088 | 0.510 | 0.102 | 0.464 | |||
CXCL1 | -0.152 | 0.296 | -0.042 | 0.773 | 0.117 | 0.271 | 0.113 | 0.300 | 0.362 | 0.064 | 0.420 | 0.033 | |||
CXCL6 | -0.200 | 0.177 | -0.133 | 0.368 | 0.047 | 0.723 | 0.030 | 0.822 | 0.421 | 0.134 | 0.361 | 0.218 | |||
IL-6 | -0.238 | 0.042 | -0.241 | 0.039 | 0.111 | 0.300 | 0.092 | 0.358 | 0.020 | 0.923 | 0.005 | 0.981 | |||
IL-8 | -0.015 | 0.878 | 0.006 | 0.951 | 0.059 | 0.448 | 0.030 | 0.705 | 0.003 | 0.986 | -0.025 | 0.892 | |||
IL-18R1 | 0.063 | 0.404 | 0.049 | 0.513 | 0.066 | 0.302 | 0.049 | 0.429 | 0.052 | 0.644 | 0.053 | 0.630 | |||
MCP-1 | 0.087 | 0.151 | 0.108 | 0.082 | 0.007 | 0.887 | 0.003 | 0.956 | -0.032 | 0.753 | -0.026 | 0.811 | |||
OPG | 0.113 | 0.034 | 0.109 | 0.049 | 0.013 | 0.788 | -0.003 | 0.954 | 0.006 | 0.956 | 0.005 | 0.961 | |||
t-PA | 0.007 | 0.974 | 0.061 | 0.785 | 0.149 | 0.463 | 0.000 | 1.000 | 0.037 | 0.910 | -0.022 | 0.944 | |||
TWEAK | -0.069 | 0.225 | -0.071 | 0.236 | 0.010 | 0.860 | -0.012 | 0.833 | 0.185 | 0.147 | 0.158 | 0.222 | |||
VEGF-A | -0.026 | 0.698 | -0.024 | 0.706 | -0.025 | 0.684 | -0.026 | 0.670 | -0.082 | 0.464 | -0.084 | 0.472 | |||
4E-BP1 | -0.065 | 0.617 | -0.083 | 0.520 | -0.025 | 0.825 | -0.036 | 0.759 | 0.186 | 0.390 | 0.156 | 0.493 |
Dominant model
Men | NEU women | EU women | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Model 1a
| Model 2b
| Model 1a
| Model 2b
| Model 1a
| Model 2b
| ||||||||||
Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| ||||
ADA | 0.024 | 0.663 | 0.022 | 0.700 | -0.032 | 0.457 | -0.022 | 0.616 | 0.024 | 0.737 | 0.026 | 0.725 | |||
AXL | 0.032 | 0.489 | 0.046 | 0.318 | -0.052 | 0.113 | -0.048 | 0.142 | 0.044 | 0.494 | 0.029 | 0.639 | |||
CCL20 | -0.263 | 0.016 | -0.241 | 0.030 | 0.051 | 0.525 | 0.027 | 0.744 | 0.142 | 0.300 | 0.136 | 0.334 | |||
CD40 | -0.096 | 0.077 | -0.072 | 0.187 | -0.062 | 0.182 | -0.062 | 0.191 | 0.059 | 0.452 | 0.080 | 0.340 | |||
CXCL1 | -0.058 | 0.553 | 0.025 | 0.802 | 0.048 | 0.481 | 0.053 | 0.451 | 0.183 | 0.116 | 0.252 | 0.033 | |||
CXCL6 | -0.141 | 0.157 | -0.083 | 0.406 | -0.021 | 0.806 | -0.016 | 0.851 | 0.312 | 0.060 | 0.292 | 0.093 | |||
IL-6 | -0.163 | 0.039 | -0.159 | 0.045 | 0.019 | 0.788 | 0.024 | 0.713 | -0.060 | 0.625 | -0.089 | 0.440 | |||
IL-8 | 0.003 | 0.966 | 0.026 | 0.704 | 0.018 | 0.719 | -0.001 | 0.984 | 0.021 | 0.837 | 0.008 | 0.938 | |||
IL-18R1 | 0.044 | 0.382 | 0.047 | 0.351 | 0.007 | 0.874 | 0.010 | 0.796 | 0.035 | 0.606 | 0.021 | 0.751 | |||
MCP-1 | 0.016 | 0.693 | 0.037 | 0.374 | -0.005 | 0.893 | -0.007 | 0.840 | -0.011 | 0.864 | -0.012 | 0.857 | |||
OPG | 0.074 | 0.040 | 0.072 | 0.054 | -0.001 | 0.970 | -0.010 | 0.756 | 0.009 | 0.895 | 0.010 | 0.885 | |||
t-PA | -0.093 | 0.535 | -0.030 | 0.840 | 0.074 | 0.570 | 0.022 | 0.862 | 0.033 | 0.869 | 0.034 | 0.861 | |||
TWEAK | -0.046 | 0.231 | -0.047 | 0.248 | 0.006 | 0.865 | -0.008 | 0.817 | 0.113 | 0.135 | 0.110 | 0.152 | |||
VEGF-A | -0.004 | 0.929 | 0.004 | 0.927 | -0.022 | 0.580 | -0.011 | 0.776 | -0.068 | 0.304 | -0.082 | 0.239 | |||
4E-BP1 | -0.007 | 0.937 | -0.013 | 0.884 | -0.054 | 0.458 | -0.047 | 0.532 | 0.069 | 0.590 | 0.062 | 0.648 |
Recessive model
Men | NEU women | EU women | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Model 1a
| Model 2b
| Model 1a
| Model 2b
| Model 1a
| Model 2b
| ||||||||||
Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| Coefficient |
p
| ||||
ADA | -0.041 | 0.632 | -0.042 | 0.636 | 0.056 | 0.456 | 0.040 | 0.612 | 0.049 | 0.740 | 0.010 | 0.951 | |||
AXL | 0.157 | 0.027 | 0.124 | 0.081 | -0.071 | 0.216 | -0.066 | 0.251 | -0.201 | 0.127 | -0.149 | 0.252 | |||
CCL20 | -0.166 | 0.333 | -0.205 | 0.234 | 0.170 | 0.227 | 0.122 | 0.407 | -0.063 | 0.823 | -0.098 | 0.740 | |||
CD40 | -0.160 | 0.058 | -0.134 | 0.112 | -0.009 | 0.917 | -0.052 | 0.535 | 0.024 | 0.882 | 0.014 | 0.938 | |||
CXCL1 | -0.195 | 0.201 | -0.151 | 0.326 | 0.149 | 0.213 | 0.121 | 0.333 | 0.387 | 0.108 | 0.344 | 0.162 | |||
CXCL6 | -0.101 | 0.519 | -0.094 | 0.544 | 0.187 | 0.207 | 0.131 | 0.392 | -0.010 | 0.977 | -0.092 | 0.802 | |||
IL-6 | -0.133 | 0.283 | -0.153 | 0.213 | 0.229 | 0.058 | 0.163 | 0.157 | 0.346 | 0.172 | 0.364 | 0.130 | |||
IL-8 | -0.039 | 0.707 | -0.047 | 0.655 | 0.096 | 0.279 | 0.080 | 0.370 | -0.099 | 0.636 | -0.139 | 0.535 | |||
IL-18R1 | 0.032 | 0.689 | -0.005 | 0.953 | 0.149 | 0.037 | 0.093 | 0.186 | 0.018 | 0.899 | 0.015 | 0.913 | |||
MCP-1 | 0.154 | 0.016 | 0.147 | 0.023 | 0.033 | 0.580 | 0.029 | 0.631 | -0.058 | 0.656 | -0.044 | 0.749 | |||
OPG | 0.071 | 0.207 | 0.067 | 0.251 | 0.037 | 0.508 | 0.024 | 0.673 | -0.018 | 0.897 | -0.092 | 0.506 | |||
t-PA | 0.243 | 0.299 | 0.206 | 0.375 | 0.150 | 0.513 | -0.070 | 0.759 | -0.023 | 0.956 | -0.242 | 0.550 | |||
TWEAK | -0.042 | 0.489 | -0.045 | 0.478 | 0.006 | 0.923 | -0.003 | 0.958 | 0.108 | 0.493 | 0.023 | 0.889 | |||
VEGF-A | -0.047 | 0.499 | -0.063 | 0.355 | 0.005 | 0.942 | -0.031 | 0.656 | 0.036 | 0.794 | 0.056 | 0.700 | |||
4E-BP1 | -0.127 | 0.353 | -0.152 | 0.263 | 0.107 | 0.401 | 0.060 | 0.652 | 0.314 | 0.238 | 0.227 | 0.422 |