Skip to main content

Table 1 Characteristics of included studies for assessment of association between genetic variants and ADRs in PD

From: A systematic review and integrative approach to decode the common molecular link between levodopa response and Parkinson’s disease

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)
  1. M male, F female, ADR Adverse drug reaction, FP Follow-up Period, AJ Ashkenazi Jews; UKPDS-BBC,UK Parkinson’s disease society Brain Bank Criteria, UPDRS Unified Parkinson’s disease rating scale; HY Hoehn and Yahr Staging of Parkinson's Disease, MMSE Mini mental state examination, AIMS Abnormal Involuntary Movement Scale, PPRS Parkinson’s Psychosis Rating Scale; PDSK,DDSK14; ADL Activities of Daily living, WHO-UMC World health organization-Uppsala Monitoring Centre, PCR-RFLP Polymerase chain reaction- Restriction fragment length polymorphism; OR Odds Ratio, CI Confidence Interval; Drugs are L-levodopa, C-carbidopa, A-amantadine, T-, DA-Dopamine Agonist, MBI-MAO-B inhibitor, S-Selegiline, R-Ropinirole, E-Entacapone, P-Pramipexole, p- pergolide; LEDD, Levodopa equivalent drug dose; NA No association, -; Insufficient data. Score- Cumulative score for Methodological Quality Assessment (Ref Additional file 4: Table S1a for detailed scoring) Odds Ratio, Prevalence Ratio and Hazard Ratio are synonymously used in the table. *OR calculated using reported frequencies from the respective article. Dose of drug are in mg/day. aUnit of Age, Dose and Follow up period are represented with Mean  ± standard deviation; Greenbaum L et al. two p-values are of Israeli and Italian, respectively. All the studies recruited PD patients diagnosed by United Kingdom Parkinson’s Disease society brain bank criteria expect $- Not reported, #- by Neurologist/PD Specialist, €- CAPIT, β- Gelb Criteria. Most of the studies followed PCR-RFLP for genotyping except t- TaqMan, s- Sequenom iPLEXTM, r- RT-PCR, a- ABI PRISM 310. Bold are significant polymorphisms (p≤ 0.05) and their corresponding genes