Table 1 Characteristics of included studies for assessment of association between genetic variants and ADRs in PD
Study | Population/ ethnicity | Response criteria | Age (years)a | Gender | Number of samples | Type of ADR | Genes | Studied variants | p- value | OR (95% CI) | Dosea (drug) | FPa (years) | Score | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
M | F | Total | ADR | Non ADR | ||||||||||||
Schuh A F S et al. [64]; t | Brazilian | UPDRS, HY, MMSE | 67.38 ± 10.34 | 105 | 100 | 205 | 86 | 119 | Dyskinesia | HOMER1 | rs4704559 | (GG/GA) 0.04 | 0.53 (0.29-0.98) * | 200 (L) | 1 | 13 |
Rieck M et al. [65]; t | Brazilian | UPDRS-IV | 66.88 ± 10.80 | 110 | 98 | 208 | 90 | 118 | Dyskinesia | ADORA2A | rs2298383 | CT-0.04 | 1.89 (1.03–3.45) | 805.14 ± 310.17 (L) | 8.34 ± 4.86 | 13 |
TT-0.02 | 2.06 (1.10–3.82) | |||||||||||||||
rs3761422 | CC-0.02 | 3.12 (1.22-7.96) | ||||||||||||||
CT-0.01 | 3.28 (1.30-8.27) | |||||||||||||||
Strong J.A et al [23]. $ | Caucasian | NR | 65.3 ± 1.56 early; 69.4 ± 1.25 late | 57 | 35 | 92 | 92 | NA | Dyskinesia | DRD2 | 14 allele | 0.04 | 3.4 (1.1-10.4) | NA (L, C) | 5 | 9 |
14/15 | 0.003 | 27.2 (1.4-51.0) | ||||||||||||||
Rieck M et.al [66] | Brazilian | UPDRS-IV | 65.52 ± 9.99 | 102 | 97 | 199 | 83 | 116 | Dyskinesia | DRD2 | rs2283265 | 0.05 | - | 780.12 ± 308.08 (L) | 8.44 ± 4.92 | 13 |
ANKK1 | rs1800497 | 0.02 | ||||||||||||||
Oliveri R.L et al. [57] | Italian | UPDRS-ME, AIMS, MMSE, Hamilton | 64.6 ± 9.4 | 53 | 45 | 98 | 49 | 49 | Dyskinesia | DRD2 | 13 | 0.02 | 0.37 (0.15- 0.89) * | 25mg (C); 250mg (L) | 5 | 13 |
14 | 0.02 | 0.25 (0.07- 0.92) * | ||||||||||||||
15 | 0.02 | 1.94 (1.08- 3.49) * | ||||||||||||||
13/16 | 0.05 | - | ||||||||||||||
15/16 | 0.01 | 3.88 (1.28- 11.74) | ||||||||||||||
Gorgone G et al. [32] | Italian | HY | 64.5 ± 7.7 (cases) | 64 | 78 | 142 | 60 cases | 82 control | Hyper-homocysteinemia | MTHFR | rs1801133 | <0.0001 | 2.59 (1.20-5.57) * | 452.0 ± 170.0 (L) | 1 | 12 |
Acuña G et al. [61] $ | European | NR | NA | 261 | 148 | 409 | 135 | 274 | Elevated liver transaminase levels | UGT1A | C908G | 0.0018 | - | NA (T, L) | NA | 7 |
T232G | 0.01060 | |||||||||||||||
A528G | 0.0008 | |||||||||||||||
A754G | 0.0023 | |||||||||||||||
A765C | 0.0023 | |||||||||||||||
A197C | 0.024 | |||||||||||||||
G551T | 0.049 | |||||||||||||||
A555C | 0.0494 | |||||||||||||||
A556G | 0.0494 | |||||||||||||||
T786C | 0.0252 | |||||||||||||||
Foltynie T et al. [45];#; t | UK Caucasian | UPDRS | 62.2 | 194 | 121 | 315 | 47 | 268 | Dyskinesia | BDNF | rs6265 | 0.001 | 2.12 (1.36-3.38) | NA (L) | 1-2 | 11 |
Kiferle L et al. [19] | Caucasian | UPDRS, MMSE, HY | 62.69±11.52 | 59 | 63 | 312 | 60 | 62 | Visual hallucinations/ Psychosis (psy.) | SLC6A4 | rs25531 | >0.01 | 0.86 (0.52-1.44) * | (L)-259 ± 117.30 (psy.), 278.2 ± 181.98 (no psy.); (DA) 2.98 ± 1.73 (psy.), 2.78 ± 1.66 (no psy.) | ≥ 4 | 13 |
HTR2A | rs6313 | >0.05 | 0.94 (0.57- 1.55) * | |||||||||||||
Stefanovic M et al. [29] $ | Croatian | HY (2.5) | 62 | 81 | 105 | 41 case, 145 control | NA | NA | Wearing on- off, Dyskinesia | CYP2D6 | *3, *4, *6, *7, and *8 | 0.03 (*4) | 2.1 (1.11-3.99) | NA (L) | NA | 5 |
De Bonisa ML et al. [36] | Italian | UPDRS, HY (1.5-3) | 71.96±4.69 (A1), 65.75±9.60 (A2), | 38 | 18 | 44 (treated) | NA | NA | Hyperhomocysteinemia | MTHFR | rs1801133 | < 0.0001 | - | NA (L) | NA | 10 |
Schuh AFS et al. [28] | Brazilian | MMSE, HY | 68.0±10.3 | 100 | 96 | 196 | 50 | 146 | Visual hallucinations | DAT1 | rs28363170 | 0.02 | 2.5 (1.13–5.5) | 793.2 ± 409.1 (L) | > 1 | 12 |
Fujii C et al. [30]; $; a | Japanese | NR | 68.2±9.2 cases, 64.0±9.0 controls | 130 | 81 | 116 case, 95 control | 23 | 93 | Hallucination | CCK | rs1799923 | 0.02 | 0.28 (0.10-0.77) * | 350.4 ± 140.7 (L) | 3.9 ± 4.5 | 10 |
Yuan RY et al.[31] | Taiwanese | HY (1-3) | 71.37 ± 9.86 | 85 | 101 | 76 cases, 110 control | 48 | 28 | Hyper-homocysteinemia | MTHFR | rs1801133 (C677T), | CT-0.004 TT-0.02 | - | 360.21 ± 137.62 (L, A, S/R) | 6.23 ± 4.33 | 11 |
rs1801131 (A1298C) | AA <0.001 AC-0.01 | - | ||||||||||||||
Paus S et al.[38] | German | HY | 64.7 ± 10.1 | 364 | 227 | 591 | 117 | 474 | Chorea | DRD3 | rs6280 | 0.0005 | - | NA (L) | NA | 13 |
92 | 499 | Dystonia | ||||||||||||||
Ivanova SA et al.[20] $ | Caucasian | AIMS | NA | NA | NA | 143 | 143 | NA | Dyskinesia | GRIN2A | NA (L, DA) | ≥ 3 | 7 | |||
rs7192557 | 0.0062 | 3.21 (1.37-7.51) | ||||||||||||||
rs8057394 | 0.0033 | 3.59 (1.48-8.71) | ||||||||||||||
De Luca V et al. [60]; t | Southern Italian | UPDRS, HY, MMSE | 70.87 ± 7.59 | 65 | 66 | 131 | 47 | 84 | Hallucination | HOMER1 | rs4704559 | 0.004 | 5.89 (1.33-26.14) * | 676.42 ± 244.38 (L) | 6 months | 12 |
rs4704560 | 0.04 | 1.79 (1.03-3.10) * | ||||||||||||||
Wu H et al. [33] | Chinese | NA | NA | 144 | 115 | 516 | 259 cases | 257 control | Wearing off | COMT | rs4680 | GA vs AA-0.01 | 6.54 (1.49-28.57) | 407.45 (Multiple) | NA | 10 |
GG vs AA-<0.001 | 8.84 (4.74-16.39) | |||||||||||||||
de Lau L M et al. [37]; t | Dutch | HY, UPDRS, MMSE | 49.9 | 143 | 76 | 219 | 98 | 121 | Dyskinesia | COMT | rs4680 | A allele-0.004 | - | (A-P M) | NA | 10 |
Zappia M et al. [59] | Italian | UPDRS, HY | 65.2 ± 8.4 | 123 | 92 | 215 | 105 | 110 | Dyskinesia | DRD2 | 13, 14 + CA n STR repeat | 0.005 | 0.45 (0.26-0.79) | 654.5 ± 289.6 (L) | 0.5 | 12 |
Kaplan N et al. [68] | Israeli | NR | 55.2 ±13.5 | 213 | 139 | 352 | 192 | 160 | Dyskinesia | SLC6A3 | rs393795 | 0.000041 | 4.96 (2.3-10.9) | NA (L) | 5 ± 4.5 | 11 |
Greenbaum L et al. [46] | Jewish Israeli, Italian | UPDRS | NR | 230 | 160 | 390 | 128 | 75 | Tardive dyskinesia | ABCC8 | rs886292 | 0.05, 0.88 | 1.63 (1–2.67), 1.03 (0.75–1.41) | NA (L) | ≥ 3 | 12 |
RYR1 | rs11880894 | 0.26, 0.03 | 0.7 (0.39–1.29), 1.26 (0.81–1.97) | |||||||||||||
DRD2 | rs1800497 | 0.53, 0.04 | 1.25 (0.63–2.48), 0.64 (0.42–0.98) | |||||||||||||