Background
Methods
Study design and population
Procedures
Genotyping of BDNF polymorphisms
Regions | Primers | Primer sequence (5′ → 3′) |
---|---|---|
rs 2883187 | Forward | GTGAGGCATCCGGCCCGGCTGGGGA |
Reverse | CGGAGCGCGGTCTCGGCAGCTCCCC | |
rs 7103873 | Forward | AGGACCTTTTACCCCCAAATGTAGA |
Reverse | ACTAAATGAAAAACCATTCTTTAAA | |
rs 7103411 | Forward | GGAGCGCACTGTAAAGATACTGATA |
Reverse | GAACACGAATGTGAGATCAATGTTG | |
rs 10835210 | Forward | CTTAACTGTAAAGCACAGGAAAGTG |
Reverse | TCATTACTTGTAGCTTAATGCAGGA | |
rs 11030104 | Forward | ATTAAAAAGCAGATAACACTACCAC |
Reverse | TACTAACTGTCCTACAATTTCCTGT | |
rs 12273539 | Forward | ACTCAATGCTTCATCACTTCTGCTC |
Reverse | GATCAGGACAGAGTCCTTGGAGTGC | |
rs 11030102 | Forward | CTACTTCTCAGTTCTGAGGCATGGA |
Reverse | TTACAAAAAGACACATACATGCAAT | |
rs 11030101 | Forward | GATACTCTATTATAGCAAAGAAGAA |
Reverse | GATAATTTCATTGAGCCATCCTGTT | |
rs 6265 | Forward | TCCTCATCCAACAGCTCTTCTATCA |
Reverse | GTGTTCGAAAGTGTCAGCCAATGAT | |
rs 7124442 | Forward | AAGGAAGCTGCATAAAGTTGACATA |
Reverse | AGCAGATATTCCAAGCATTCCTTAC |
Statistical analysis
Results
BDNF genotypes and alleles and their association with clinical measurements
Marker | Genotype/allele | Contol, n (%) | Fibromyalgia, n (%) | Exact p valueb | OR (95% CI), p valuec | OR (95% CI), p value, adjusted by age, sex‡ |
---|---|---|---|---|---|---|
rs2883187 | C/C | 115 (27.5) | 100 (24.4) | 0.218 | 1 | 1 |
C/T | 220 (52.6) | 208 (50.9) | 1.087 (0.783–1.510), p = 0.617 | 1.044 (0.747–1.458), p = 0.802 | ||
T/T | 83 (19.9) | 101 (24.7) | 1.399 (0.943–2.078), p = 0.096 | 1.340 (0.897–2.002), p = 0.152 | ||
C | 450 (53.8) | 408 (49.9) | 0.119 | 1 | ||
T | 386 (46.2) | 410 (50.1) | 1.172 (0.966–1.421), p = 0.108 | 1.147 (0.943–1.395), p = 0.171 | ||
rs7103873 | G/G | 113 (27.8) | 98 (24.0) | 0.245 | 1 | 1 |
C/G | 210 (51.6) | 208 (51.0) | 1.142 (0.820–1.591), p = 0.432 | 1.110 (0.791–1.556), p = 0.546 | ||
C/C | 84 (20.6) | 102 (25.0) | 1.400 (0.943–2.080), p = 0.095 | 1.345 (0.899–2.010), p = 0.149 | ||
G | 436 (53.6) | 404 (49.5) | 0.112 | 1 | ||
C | 378 (46.4) | 412 (50.5) | 1.176 (0.968–1.429), p = 0.102 | 1.153 (0.946–1.405), p = 0.158 | ||
rs7103411 | C/C | 120 (28.5) | 128 (31.3) | 0.638 | 1 | 1 |
C/T | 208 (49.4) | 198 (48.4) | 0.892 (0.651–1.224), p = 0.48 | 0.884 (0.641–1.220), p = 0.454 | ||
T/T | 93 (22.1) | 83 (20.3) | 0.837 (0.568–1.232), p = 0.366 | 0.865 (0.584–1.280), p = 0.468 | ||
C | 448 (53.2) | 454 (55.5) | 0.374 | 1 | ||
T | 394 (46.8) | 364 (44.5) | 0.912 (0.751–1.106), p = 0.348 | 0.925 (0.76–1.125), p = 0.435 | ||
rs10835210 | C/C | 204 (49.4) | 196 (48.0) | 0.725 | 1 | 1 |
A/C | 175 (42.4) | 172 (42.2) | 1.023 (0.767–1.364), p = 0.877 | 0.991 (0.740–1.326), p = 0.949 | ||
A/A | 34 (8.2) | 40 (9.8) | 1.224 (0.745–2.014), p = 0.425 | 1.183 (0.714–1.957), p = 0.514 | ||
C | 583 (70.6) | 564 (69.1) | 0.554 | 1 | ||
A | 243 (29.4) | 252 (30.9) | 1.072 (0.868–1.324), p = 0.518 | 1.048 (0.846–1.297), p = 0.671 | ||
rs11030104 | A/A | 101 (24.0) | 126 (31.0) | 0.031 | 1 | 1 |
A/G | 205 (48.8) | 196 (48.2) | 0.766 (0.553–1.063), p = 0.111 | 0.758 (0.544–1.057), p = 0.102 | ||
G/G | 114 (27.1) | 85 (20.9) | 0.598 (0.407–0.877), p = 0.009 | 0.619 (0.419–0.913), p = 0.016 | ||
A | 407 (48.5) | 448 (55.0) | 0.009 | 1 | ||
G | 433 (51.5) | 366 (45.0) | 0.768 (0.633–0.932), p = 0.007 | 0.781 (0.641–0.95), p = 0.013 | ||
rs12273539 | C/C | 283 (67.1) | 268 (65.4) | 0.101 | 1 | 1 |
C/T | 132 (31.3) | 125 (30.5) | 1 (0.744–1.345), p = 1 | 1.009 (0.747–1.362), p = 0.955 | ||
T/T | 7 (1.7) | 17 (4.1) | 2.564 (1.047–6.282), p = 0.039 | 2.586 (1.052–6.36), p = 0.038 | ||
C | 698 (82.7) | 661 (80.6) | 0.299 | 1 | ||
T | 146 (17.3) | 159 (19.4) | 1.150 (0.897–1.475), p = 0.27 | 1.161 (0.902–1.493), p = 0.246 | ||
rs11030102 | C/C | 419 (99.3) | 402 (98.5) | 0.334 | 1 | 1 |
C/G | 3 (0.7) | 6 (1.5) | 2.085 (0.518–8.392), p = 0.301 | 2.129 (0.524–8.649), p = 0.291 | ||
C | 841 (99.6) | 810 (99.3) | 0.335 | 1 | ||
G | 3 (0.4) | 6 (0.7) | 2.077 (0.518–8.326), p = 0.302 | 2.12 (0.524–8.58), p = 0.292 | ||
rs11030101 | A/A | 208 (49.5) | 197 (48.3) | 0.752 | 1 | 1 |
A/T | 178 (42.4) | 172 (42.2) | 1.020 (0.766–1.358), p = 0.891 | 0.985 (0.737–1.317), p = 0.92 | ||
T/T | 34 (8.1) | 39 (9.6) | 1.211 (0.735–1.996), p = 0.452 | 1.152 (0.694–1.912), p = 0.583 | ||
A | 594 (70.7) | 566 (69.4) | 0.585 | 1 | ||
T | 246 (29.3) | 250 (30.6) | 1.067 (0.864–1.316), p = 0.548 | 1.036 (0.837–1.283), p = 0.743 | ||
rs6265 | G/G | 96 (22.9) | 87 (21.3) | 0.770 | 1 | 1 |
A/G | 204 (48.7) | 197 (48.3) | 1.066 (0.751–1.512), p = 0.722 | 1.017 (0.712–1.451), p = 0.928 | ||
A/A | 119 (28.4) | 124 (30.4) | 1.150 (0.783–1.688), p = 0.476 | 1.110 (0.752–1.638), p = 0.599 | ||
G | 396 (47.3) | 371 (45.5) | 0.496 | 1 | ||
A | 442 (52.7) | 445 (54.5) | 1.075 (0.886–1.304), p = 0.466 | 1.058 (0.869–1.287), p = 0.575 | ||
rs7124442 | C/C | 2 (0.5) | 0 (0) | 0.574 | 1 | 1 |
C/T | 51 (12.1) | 47 (11.5) | 718,117.521 (0-Inf), p = 0.972 | 683,123.831 (0-Inf), p = 0.972 | ||
T/T | 368 (87.4) | 360 (88.5) | 762,294.038 (0-Inf), p = 0.971 | 682,163.974 (0-Inf), p = 0.972 | ||
C | 55 (6.5) | 47 (5.8) | 0.590 | 1 | ||
T | 787 (93.5) | 767 (94.2) | 1.140 (0.763–1.705), p = 0.521 | 1.078 (0.716–1.623), p = 0.72 |
Position | Genotype | Numbera | Tender point number | Tender point count | FIQ | BFI | PCS | MCS | BDI | STAI-I | STAI-II |
---|---|---|---|---|---|---|---|---|---|---|---|
rs2883187 | C/C | 100 | 13.38 (12.21–14.56) | 25.17 (21.2–29.14) | 58.56 (53.23–63.9) | 7.25 (5.28–9.22) | 38.02 (35.88–40.16) | 31.25 (27.83–34.67) | 18.09 (15.05–21.12) | 51.56 (48.06–55.06) | 51.97 (48.73–55.21) |
C/T | 208 | 13.80 (12.83–14.77) | 25.70 (22.43–28.96) | 610 (56.69–65.32) | 6.27 (4.66–7.89) | 37.29 (35.56–39.03) | 32.62 (29.85–35.39) | 18.57 (16.11–21.02) | 49.73 (46.9–52.56) | 50.2 (47.59–52.81) | |
T/T | 101 | 13.77 (12.54–15.0) | 25.85 (21.68–30.03) | 58.21 (52.66–63.77) | 7.16 (5.11–9.22) | 38.17 (35.94–40.41) | 34.26 (30.69–37.83) | 16.89 (13.7–20.08) | 49.49 (45.82–53.15) | 48.29 (44.9–51.68) | |
p value† | 0.739 | 0.947 | 0.449 | 0.466 | 0.625 | 0.299 | 0.54 | 0.478 | 0.138 | ||
rs7103873 | G/G | 98 | 13.37 (12.18–14.55) | 25.01 (21.01–29.01) | 57.96 (52.56–63.35) | 7.34 (5.35–9.32) | 37.96 (35.8–40.12) | 31.39 (27.93–34.85) | 17.78 (14.71–20.85) | 51.52 (47.98–55.06) | 51.9 (48.63–55.18) |
G/C | 208 | 13.84 (12.88–14.81) | 25.97 (22.73–29.21) | 60.89 (56.60–65.19) | 6.25 (4.65–7.85) | 37.34 (35.62–39.07) | 32.83 (30.07–35.6) | 18.45 (16.01–20.9) | 49.51 (46.7–52.32) | 50.08 (47.48–52.68) | |
C/C | 102 | 13.66 (12.42–14.9) | 25.28 (21.08–29.49) | 59.04 (53.43–64.64) | 7.26 (5.19–9.33) | 38.07 (35.82–40.32) | 33.52 (29.92–37.13) | 17.4 (14.18–20.62) | 50.33 (46.64–54.02) | 48.72 (45.31–52.13) | |
p valueb | 0.69 | 0.857 | 0.479 | 0.389 | 0.721 | 0.523 | 0.755 | 0.484 | 0.224 | ||
rs7103411 | C/C | 128 | 13.79 (12.68–14.9) | 25.97 (22.21–29.72) | 60.26 (55.22–65.3) | 6.97 (5.11–8.83) | 37.76 (35.73–39.79) | 32.88 (29.64–36.12) | 18.25 (15.37–21.14) | 50.48 (47.17–53.8) | 49.28 (46.21–52.35) |
C/T | 198 | 13.74 (12.74–14.74) | 25.65 (22.27–29.02) | 60.54 (56.09–64.99) | 6.07 (4.41–7.73) | 37.5 (35.71–39.29) | 33.0 (30.14–35.87) | 18.32 (15.78–20.85) | 49.55 (46.62–52.47) | 50.44 (47.74–53.15) | |
T/T | 83 | 13.46 (12.23–14.68) | 25.0 (20.87–29.14) | 57.81 (52.24–63.38) | 7.64 (5.59–9.68) | 37.79 (35.55–40.02) | 31.41 (27.84–34.98) | 17.5 (14.33–20.67) | 50.89 (47.22–54.55) | 51.09 (47.69–54.48) | |
p valueb | 0.859 | 0.907 | 0.582 | 0.249 | 0.947 | 0.635 | 0.86 | 0.705 | 0.578 | ||
rs10835210 | C/C | 196 | 13.49 (12.50–14.47) | 25.67 (22.37–28.97) | 59.70 (55.30–64.10) | 6.91 (5.27–8.55) | 37.78 (36.02–39.55) | 31.77 (28.96–34.58) | 18.87 (16.37–21.36) | 51.04 (48.18–53.9) | 51.77 (49.13–54.41) |
C/A | 172 | 13.87 (12.84–14.91) | 25.51 (22.04–28.99) | 60.15 (55.46–64.85) | 6.66 (4.93–8.4) | 37.3 (35.41–39.18) | 33.19 (30.18–36.2) | 17.17 (14.5–19.83) | 48.42 (45.35–51.48) | 48.63 (45.81–51.45) | |
A/A | 40 | 13.96 (12.18–15.74) | 24.85 (18.87–30.83) | 59.67 (51.64–67.7) | 5.46 (2.52–8.4) | 38.45 (35.22–41.67) | 35.31 (30.17–40.45) | 17.78 (13.17–22.4) | 51.79 (46.49–57.08) | 47.51 (42.62–52.4) | |
p valueb | 0.675 | 0.962 | 0.977 | 0.609 | 0.728 | 0.301 | 0.384 | 0.138 | 0.029 | ||
rs11030104 | A/A | 126 | 13.80 (12.68–14.92) | 25.99 (22.22–29.75) | 60.27 (55.2–65.35) | 7.0 (5.13–8.87) | 37.82 (35.77–39.86) | 32.86 (29.6–36.12) | 18.33 (15.43–21.23) | 50.46 (47.13–53.79) | 49.29 (46.2–52.37) |
A/G | 196 | 13.79 (12.79–14.8) | 25.67 (22.3–29.03) | 60.66 (56.19–65.13) | 6.09 (4.42–7.76) | 37.4 (35.60–39.20) | 32.9 (30.02–35.77) | 18.41 (15.87–20.95) | 49.69 (46.76–52.61) | 50.53 (47.82–53.24) | |
G/G | 85 | 13.31 (12.08–14.53) | 24.75 (20.64–28.86) | 57.55 (51.98–63.12) | 7.58 (5.53–9.62) | 37.86 (35.63–40.1) | 31.6 (28.03–35.16) | 17.31 (14.15–20.47) | 50.63 (46.99–54.28) | 50.88 (47.49–54.27) | |
p valueb | 0.677 | 0.845 | 0.498 | 0.274 | 0.871 | 0.731 | 0.757 | 0.821 | 0.616 | ||
rs12273539 | C/C | 268 | 13.63 (12.7–14.55) | 25.24 (22.11–28.37) | 59.03 (54.81–63.25) | 6.51 (4.95–8.07) | 37.67 (35.98–39.37) | 33.14 (30.42–35.86) | 17.45 (15.05–19.85) | 49.9 (47.14–52.66) | 49.52 (46.96–52.09) |
C/T | 125 | 14.13 (13.01–15.24) | 27.04 (23.26–30.81) | 62.11 (57.15–67.08) | 6.75 (4.89–8.61) | 37.48 (35.48–39.47) | 31.56 (28.36–34.76) | 19.34 (16.5–22.18) | 50.66 (47.4–53.92) | 51.73 (48.7–54.75) | |
T/T | 17 | 11.90 (9.7–14.1) | 21.96 (14.52–29.41) | 57.64 (47.31–67.96) | 8.92 (5.15–12.69) | 38.13 (33.98–42.27) | 31.82 (25.17–38.48) | 20.22 (14.35–26.09) | 49.54 (42.8–56.29) | 50.87 (44.61–57.14) | |
p valueb | 0.131 | 0.319 | 0.349 | 0.432 | 0.945 | 0.533 | 0.26 | 0.862 | 0.271 | ||
rs11030102 | C/C | 402 | 13.67 (12.8–14.55) | 25.57 (22.61–28.53) | 59.83 (55.89–63.77) | 6.62 (5.17–8.07) | 37.66 (36.07–39.25) | 32.67 (30.14–35.21) | 18.06 (15.83–20.29) | 50.02 (47.45–52.59) | 50.16 (47.78–52.55) |
C/G | 6 | 17.58 (13.01–22.15) | 36.13 (20.73–51.54) | 72.91 (51.53–94.29) | 19.07 (11.35–26.79) | 35.01 (26.4–43.63) | 23.8 (10.04–37.56) | 29.58 (17.47–41.69) | 65.06 (51.13–78.99) | 62.56 (49.62–75.51) | |
p valueb | 0.089 | 0.172 | 0.224 | 0.001 | 0.542 | 0.2 | 0.059 | 0.032 | 0.057 | ||
rs11030101 | A/A | 197 | 13.49 (12.51–14.47) | 25.69 (22.38–29.01) | 59.82 (55.43–64.22) | 6.91 (5.27–8.55) | 37.79 (36.02–39.55) | 31.73 (28.92–34.54) | 18.94 (16.45–21.43) | 51.01 (48.15–53.87) | 51.77 (49.13–54.42) |
A/T | 172 | 13.84 (12.81–14.87) | 25.38 (21.9–28.87) | 60.26 (55.57–64.95) | 6.69 (4.95–8.43) | 37.34 (35.45–39.22) | 33.14 (30.14–36.15) | 17.1 (14.43–19.76) | 48.41 (45.34–51.48) | 48.57 (45.75–51.4) | |
T/T | 39 | 14.23 (12.45–16.01) | 26.37 (20.36–32.37) | 58.75 (50.73–66.77) | 5.33 (2.39–8.27) | 38.16 (34.93–41.39) | 35.94 (30.8–41.08) | 17.66 (13.12–22.21) | 52.15 (46.94–57.37) | 48.07 (43.25–52.89) | |
p valueb | 0.605 | 0.943 | 0.929 | 0.555 | 0.816 | 0.212 | 0.325 | 0.126 | 0.033 | ||
rs6265 | G/G | 87 | 13.29 (12.07–14.51) | 24.66 (20.55–28.78) | 57.67 (52.14–63.21) | 7.55 (5.52–9.59) | 37.83 (35.61–40.06) | 31.56 (28.01–35.11) | 17.44 (14.29–20.59) | 50.62 (46.97–54.26) | 50.94 (47.56–54.32) |
G/A | 197 | 13.77 (12.77–14.77) | 25.62 (22.26–28.99) | 60.72 (56.27–65.18) | 6.11 (4.44–7.77) | 37.45 (35.65–39.24) | 32.92 (30.05–35.79) | 18.27 (15.74–20.81) | 49.6 (46.67–52.52) | 50.43 (47.71–53.14) | |
A/A | 124 | 13.88 (12.76–15) | 26.34 (22.56–30.13) | 60.17 (55.09–65.24) | 6.98 (5.11–8.86) | 37.83 (35.79–39.88) | 32.91 (29.64–36.18) | 18.37 (15.47–21.28) | 50.58 (47.24–53.91) | 49.37 (46.28–52.46) | |
p valueb | 0.634 | 0.746 | 0.513 | 0.293 | 0.898 | 0.702 | 0.829 | 0.766 | 0.657 | ||
rs7124442 | C/T | 47 | 13.57 (12.12–15.03) | 26.18 (21.3–31.07) | 62.15 (55.49–68.81) | 5.60 (3.16–8.05) | 37.37 (34.69–40.05) | 30.74 (26.46–35.03) | 19.98 (16.2–23.76) | 50.67 (46.27–55.07) | 51.35 (47.3–55.39) |
T/T | 360 | 13.72 (12.81–14.62) | 25.53 (22.48–28.57) | 59.53 (55.49–63.57) | 6.88 (5.37–8.39) | 37.69 (36.06–39.32) | 32.94 (30.34–35.54) | 17.81 (15.51–20.1) | 50.01 (47.36–52.66) | 50.04 (47.58–52.5) | |
p valueb | 0.836 | 0.777 | 0.411 | 0.274 | 0.804 | 0.285 | 0.23 | 0.755 | 0.501 |
Haplotype frequencies and clinical measurements
Combined allelesa | All subjects | Controls | Fibromyalgia | p valueb |
---|---|---|---|---|
TGACCGCTGC | 29.6 ± 0.75 | 20.22 ± 0.9 | 38.87 ± 0.88 | 0.0001 |
TATCCAACCT | 20.16 ± 0.44 | 12.94 ± 0.57 | 27.29 ± 0.52 | |
TGACCACTGC | 14.8 ± 0.75 | 25.26 ± 0.89 | 4.47 ± 0.88 | |
TAACTACCCT | 11.97 ± 0.42 | 6.99 ± 0.5 | 16.89 ± 0.53 | |
TATCCGACCT | 8.94 ± 0.45 | 15.76 ± 0.59 | 2.21 ± 0.52 | |
TAACTGCCCT | 5.74 ± 0.42 | 9.8 ± 0.5 | 1.72 ± 0.53 | |
CAACCACCGC | 3.20 ± 0.17 | 2.06 ± 0.22 | 4.33 ± 0.24 |
Combined alleles | Controls, n (%) | Fibromyalgia, n (%) | Crude OR (95% CI) | p valueb | Age and sex adjusted OR (95% CI) | p valueb |
---|---|---|---|---|---|---|
TGACCGCTGC | 193 (26.6) | 340 (45) | 1.0 (reference) | 1.0 (reference) | ||
TATCCAACCT | 119 (16.4) | 232 (30.7) | 1.107 (0.834–1.469) | 0.483 | 1.106 (0.833–1.47) | 0.487 |
TGACCACTGC | 160 (22) | 1 (0.1) | 0.004 (0–0.026) | < 0.001 | 0.004 (0.0–0.026) | < 0.001 |
TAACTACCCT | 66 (9.1) | 146 (19.3) | 1.256 (0.894–1.765) | 0.19 | 1.248 (0.887–1.756) | 0.204 |
TATCCGACCT | 103 (14.2) | 0 (0) | 0 (0-Inf) | 0.963 | 0 (0-Inf) | 0.963 |
TAACTGCCCT | 65 (9) | 0 (0) | 0 (0-Inf) | 0.971 | 0 (0-Inf) | 0.97 |
CAACCACCGC | 20 (2.8) | 37 (4.9) | 1.05 (0.593–1.861) | 0.867 | 1.088 (0.612–1.934) | 0.774 |
Combined alleles | Numbera | Tender point number | Tender point count | FIQ | BFI | PCS | MCS | BDI | STAI-I | STAI-II |
---|---|---|---|---|---|---|---|---|---|---|
TGACCGCTGC | 340 | 13.61 (12.89–14.33) | 25.33 (22.93–27.73) | 59.67 (56.48–62.87) | 6.81 (5.6–8.01) | 37.56 (36.25–38.87) | 32.12 (30.06–34.18) | 18.02 (16.22–19.83) | 50.66 (48.56–52.76) | 51.01 (49.07–52.95) |
TATCCAACCT | 232 | 13.91 (13.1–14.72) | 25.29 (22.6–27.99) | 59.88 (56.26–63.5) | 6.35 (4.99–7.71) | 37.49 (36–38.98) | 33.88 (31.54–36.21) | 17.25 (15.21–19.3) | 49.31 (46.92–51.69) | 48.26 (46.07–50.46) |
TAACTACCCT | 146 | 13.66 (12.75–14.58) | 26.34 (23.29–29.38) | 61.2 (57.17–65.23) | 7.32 (5.8–8.85) | 37.49 (35.84–39.15) | 31.73 (29.13–34.33) | 19.5 (17.21–21.78) | 50.49 (47.83–53.14) | 51.16 (48.71–53.6) |
CAACCACCGC | 37 | 13.53 (12.02–15.05) | 25.96 (20.93–31) | 63.17 (56.22–70.11) | 5.67 (3.09–8.25) | 37.78 (34.92–40.63) | 30.7 (26.22–35.18) | 20.06 (16.15–23.97) | 52.65 (48.1–57.2) | 52.74 (48.54–56.93) |
p valueb | 0.874 | 0.902 | 0.696 | 0.527 | 0.998 | 0.271 | 0.221 | 0.459 | 0.027 |