Background
Results
The TLR-6/1/10 region and investigated SNPs
TLR-6/1/10 SNPs are associated with age
German cohort | Lithuanian cohort | |||||
---|---|---|---|---|---|---|
All | Age < 50 | Age ≥ 50 | All | Age < 50 | Age ≥ 50 | |
N = 1388 |
N = 865 |
N = 523 |
N = 1028 |
N = 772 |
N = 256 | |
Mean age | 43.3 | 30.09 | 65.43 | 42.6 | 37.4 | 58.4 |
SD | 18.8 | 7.3 | 8.3 | 11.7 | 7.2 | 7.7 |
Age range | 19–49 | 50–81 | 25–49 | 50–84 | ||
Male/female | 768/620 | 394/471 | 374/149 | 631/397 | 516/256 | 115/141 |
German cohort | Young subjects (Age < 50, n = 866) | Old subjects (Age ≥ 50, n = 523) |
P-value | ||||
Wt (%) | Het (%) | Hom (%) | Wt (%) | Het (%) | Hom (%) | ||
TLR-6 (P249S)a
| 336 (38.8) | 399 (46.1) | 130 (24.9) | 158 (30.2) | 256 (48.9) | 109 (20.8) |
0.001
|
TLR-1 | 70 | 300 | 495 | 15 | 184 | 324 |
<0.001
|
prom. | (8.1) | (34.6) | (57.2) | (2.9) | (35.2) | (62.0) | |
TLR-1 | 68 | 303 | 494 | 15 | 173 | 335 |
<0.001
|
(N248S) | (7.9) | (35.0) | (57.0) | (2.9) | (33.1) | (64.1) | |
TLR-1 | 91 | 329 | 445 | 21 | 186 | 316 |
<0.001
|
(I602S) | (10.5) | (38.0) | (52.4) | (4.0) | (35.6) | (60.4) | |
TLR-10 | 603 | 231 | 31 | 371 | 142 | 10 | 0.205 |
(V775L) | (69.6) | (26.7) | (3.6) | (70.9) | (27.2) | (1.9) | |
Lithuanian cohort | Young subjects (Age < 50) | Old subjects (Age ≥ 50) |
P-value | ||||
Wt (%) | Het (%) | Hom (%) | Wt (%) | Het (%) | Hom (%) | ||
TLR-6 (P249S) | 319 | 336 | 106 | 97 | 114 | 38 | 0.689 |
(n = 761, n = 250) | (41.9) | (44.2) | (13.9) | (38.8) | (45.6) | (15.2) | |
TLR-1 prom. | 25 | 222 | 515 | 4 | 52 | 194 |
0.009
|
(n = 762, n = 250) | (3.3) | (29.1) | (67.6) | (1.6) | (20.8) | (77.6) | |
TLR-1 (N248S) | 24 | 220 | 525 | 3 | 52 | 198 |
0.008
|
(n = 769, n = 251) | (3.1) | (28.6) | (68.3) | (1.2) | (20.7) | (78.9) | |
TLR-1 (I602S) | 29 | 242 | 498 | 7 | 58 | 189 |
0.018
|
(n = 762, n = 250 | (3.8) | (31.8) | (65.4) | (2.8) | (23.2) | (75.6) | |
TLR-10 (V775L) | 575 | 166 | 7 | 209 | 38 | 1 |
0.044
|
(n = 748, n = 248) | (76.9) | (22.2) | (0.9) | (84.3) | (15.3) | (0.4) |
Predictor German cohort | Male | Female | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
β | S.E | R2
| P | 95 % CI | β | S.E | R2
| P | 95 % CI | |
TLR6 (249S/S) | −0.69 | 0.75 | 0.001 | 0.122 | −2.17–0.78 | −1.20 | 0.77 | 0.002 | 0.355 | −2.71–0.32 |
TLR-1 prom | 2.24 | 1.13 | 0.004 |
0.039
| 0.12–4.56 | 0.81 | 1.12 | 0.001 | 0.470 | −1.39–3.01 |
TLR-1 (248 S/S) | 2.38 | 1.13 | 0.004 |
0.036
| 0.80–4.05 | 2.02 | 1.13 | 0.004 | 0.074 | 0.80–4.05 |
TLR-1 (602 S/S) | 2.68 | 1.05 | 0.007 |
0.014
| 0.55–4.82 | 2.57 | 1.09 | 0.008 |
0.015
| 0.51–4.63 |
TLR-10 (775 V/V) | −0.39 | 1.28 | 0.001 | 0.760 | −2.89–2.11 | −0.39 | 1.33 | 0.001 | 0.770 | −3.00–2.22 |
Lithuanian cohort | ||||||||||
TLR6 (249S/S) | 0.97 | 0.61 | 0.002 | 0.112 | −0.23–2.16 | −0.97 | 0.91 | 0.001 | 0.288 | −2.77–0.83 |
TLR-1 prom | 1.11 | 0.82 | 0.001 | 0.178 | −0.51–2.72 | 3.41 | 1.15 | 0.020 |
0.003
| 1.15–5.67 |
TLR-1 (248 S/S) | 1.08 | 0.82 | 0.001 | 0.189 | −0.53–2.66 | 3.56 | 1.17 | 0.021 |
0.003
| 1.26–5.86 |
TLR-1 (602 S/S) | 1.33 | 0.79 | 0.003 | 0.093 | −0.22–2.87 | 2.36 | 1.10 | 0.009 |
0.032
| 0.20–4.51 |
TLR-10 (775 V/V) | −1.10 | 0.96 | 0.001 | 0.254 | −2.99–0.79 | −4.13 | 1.53 | 0.016 |
0.007
| −7.12–1.13 |
Combined | ||||||||||
TLR6 (249S/S) | 1.88 | 0.61 | 0.006 |
0.002
| 0.70–3.07 | 0.74 | 0.74 | 0.001 | 0.310 | −0.70–2.19 |
TLR-1 prom | 1.05 | 0.76 | 0.001 | 0.170 | −0.45–2.54 | 2.40 | 0.85 | 0.007 |
0.005
| 0.74–4.06 |
TLR-1(248 S/S | 1.03 | 0.76 | 0.001 | 0.176 | −0.46–2.52 | 3.24 | 0.85 | 0.013 |
0.001
| 1.56–4.91 |
TLR-1 (602 S/S) | 1.21 | 0.73 | 0.001 | 0.096 | −0.22–2.64 | 3.24 | 0.80 | 0.015 |
0.032
| 1.68–4.80 |
TLR-10 (775 V/V) | 0.21 | 0.87 | 0.001 | 0.813 | −1.50–1.19 | −2.25 | 1.05 | 0.004 |
0.032
| −4.30–0.20 |
Homozygous loss-of-function genotypes are more frequent in the Elderly
Male | Female | |||
---|---|---|---|---|
German | Odds ratio (95 % CI) |
P-value | Odds ratio (95 % CI) |
P-value |
TLR-6 (249S/S) | 1.41 (0.98–2.04) | 0.067 | 1.56 (0.97–2.50) | 0.066 |
TLR-1 prom. | 1.31 (0.98–1.76) | 0.065 | 1.02 (0.70–1.48) | 0.93 |
TLR-1 (248S/S) | 1.36 (1.02–1.81) |
0.038
| 1.31 (0.90-1.92) | 0.17 |
TLR-1 (602S/S) | 1.41 (1.06–1.87) |
0.02
| 1.53 (1.05–2.23) |
0.027
|
TLR-10 (775 V/V) | 1.05 (0.77–1.44) | 0.741 | 1.01 (0.69–1.54) | 0.89 |
Lithuanian | ||||
TLR-6 (249S/S) | 1.53 (0.89–2.62) | 0.123 | 0.88 (0.65–1.89) | 0.394 |
TLR-1 prom. | 1.46 (0.91–2.36) | 0.117 | 1.44 (1.13–1.83) |
0.003
|
TLR-1 (248S/S) | 1.42 (0.88–2.83) | 0.152 | 2.12 (1.30–3.43) |
0.002
|
TLR-1 (602S/S) | 1.77 (1.09–2.86) |
0.02
| 1.62 (1.04–2.53) |
0.033
|
TLR-10 (775 V/V) | 0.13 (0.36–1.14) | 0.132 | 0.52 (0.31–0.89) |
0.016
|
Combined | ||||
TLR-6 (249S/S) | 1.54 (1.15–2.05) |
0.003
| 1.16 (0.79–1.68) | 0.44 |
TLR-1 prom. | 1.12 (0.89–1.41) | 0.34 | 1.41 (1.06–1.89) |
0.018
|
TLR-1 (248S/S) | 1.13 (0.89–1.42) | 0.32 | 1.66 (1.24–2.23) |
0.001
|
TLR-1 (602S/S) | 1.18 (0.94–1.48) | 0.15 | 1.64 (1.28–2.19) |
0.001
|
TLR-10 (775 V/V) | 0.97 (0.75–1.25) | 0.79 | 0.73 (0.54–1.01) | 0.05 |
Combined cohort | Male | Female | ||
---|---|---|---|---|
TLR-6 (249 S/S) | Odds ratio (95 % CI) |
P-value | Odds ratio (95 % CI) |
P-value |
50–64 years | 1.52 (1.07–2.15) |
0.019
| 1.51 (0.99–2.30) | 0.056 |
65–74 years | 1.47 (0.94–2.29) | 0.093 | 0.55 (0.23–1.29) | 0.170 |
75–85 years | 1.83 (0.98–3.43) | 0.059 | 0.91 (0.37–2.20) | 0.827 |
TLR-1 prom. | ||||
50–64 years | 1.17 (0.88–1.56) | 0.271 | 1.79 (1.24–2.57) |
0.002
|
65–74 years | 1.03 (0.71–1.48) | 0.889 | 1.11 (0.66–1.85) | 0.697 |
75–85 years | 1.11 (0.64–1.93) | 0.707 | 0.90 (0.49–1.67) | 0.742 |
TLR-1 (248S/S) | ||||
50–64 years | 1.22 (0.91–1.62) | 0.180 | 1.85 (1.28–2.66) |
0.001
|
65–74 years | 1.01 (0.70–1.46) | 0.946 | 1.49 (0.87–2.54) | 0.149 |
75–85 years | 1.02 (0.59–1.76) | 0.947 | 1.31 (0.69–2.49) | 0.407 |
TLR-1 (602S/S) | ||||
50–64 years | 1.33 (1.00–1.76) |
0.047
| 1.76 (1.25–2.50) |
0.001
|
65–74 years | 1.09 (0.76–1.56) | 0.647 | 1.50 (0.90–2.49) | 0.122 |
75–85 years | 0.87 (0.51–1.47) | 0.591 | 1.45 (0.77–2.73) | 0.245 |
TLR-10 (775 V/V) | ||||
50–64 years | 0.99 (0.73–1.36) | 0.971 | 0.69 (0.46–1.01) | 0.057 |
65–74 years | 1.12 (0.76–1.669 | 0.569 | 0.65 (0.36–1.17) | 0.149 |
75–85 years | 1.01 (0.55–1.85) | 0.98 | 1.11 (0.58–2.13) | 0.763 |