Background
Methods
Subjects and clinical measures
DNA samples
Assay design and polymerase chain reaction optimization
SNP
|
Chromosome
|
Location
|
Allele changes
|
Amino acid changes
|
Forward primer (5′➔3′)
|
Reverse primer (5′➔3′)
|
Amplicon size (bp)
|
---|---|---|---|---|---|---|---|
DRD1
rs4532
| chr 5 (q35.2) | 19681423 | C > T | Nil | GAACAGAGAAGTCCCTCTCCAC | CTGGAAATCTGACTGACCCCTA | 147 |
DRD1
rs4867798
| chr 5 (q35.2) | 19679572 | T > C | Nil | GGGCTCTTCTTAAGTTGGCTTT | GGACACAGATAAATGCAAGGTG | 189 |
DRD1
rs265981
| chr 5 (q35.2) | 174870940 | T > C | Nil | GCTCTCTCCCAAGGAAGCTC | GTGCGTTTGGGGAAAGGATC | 141 |
DRD2/ANKK1
rs1800497
| chr 11 (q23.2) | 16833244 | C > T | Glu > Lys | CTCTAGGAAGGACATGATGCCC | GCAACACAGCCATCCTCAAAG | 128 |
DRD2
rs104894220
| chr 11 (q23.2) | 16850073 | G > A | Val > Ile | CATGCCCATGCTGTACAATACG | GTACCTGCGTTATTGAGTCCGA | 126 |
DRD2
rs144999500
| chr 11 (q23.2) | 16845792 | G > A | Pro > Leu | GAGCATCTGAGTGGCTTTCTTCTC | GAGAAGAATGGGCATGCCAAAG | 150 |
DRD3
rs3732783
| chr 3 (q13.31) | 20385935 | T > C | Ala > Ala | AGTAGGAGAGGGCATAGTAGGC | CTGGGCTATGGCATCTCTGAG | 116 |
DRD3
rs6280
| chr 3 (q13.31) | 20385961 | C > T | Gly > Ser | AGTAGGAGAGGGCATAGTAGGC | CTGGGCTATGGCATCTCTGAG | 116 |
DRD4
rs1800443
| chr 11 (p15.5) | 579830 | T > G | Val > Gly | TACTGTGCGGCCTCAACGAC | GGGTAGGAAGAAGGAGCACAC | 104 |
DRD5
rs144132215
| chr 4 (p16.1) | 966018 | G > T | Gly > Trp | GTCCATCCTCATCTCCTTCATTCC | CTGGAGTCACAGTTCTCTGCAT | 159 |
GRIN2B
rs7301328
| chr 12 (p13.1) | 6778901 | G > C | Pro > Pro | CTCCCTGCAGCCCCTTTTTA | CGCCCAGATCCTCGATTTCA | 109 |
High resolution melting-Polymerase chain reaction
Sequencing
Data and statistical analysis
Results
Demographic analysis of subjects
Variables
|
Control (n = 39)
|
Case (n = 52)
|
---|---|---|
Age
| ||
Mean ± SE | 63.46 ± 1.344 | 62.42 ± 1.087 |
Median | 63.00 | 63.00 |
Range | 42 - 85 | 42 - 77 |
Duration of PD
| ||
Mean ± SE | 5.77 ± 0.745 | 8.17 ± 0.725 |
Median | 4.00 | 8.00 |
Range | 1.0 - 20.0 | 0.0 - 23.0 |
Gender, n (%)
| ||
Male | 27 (69) | 38 (73) |
Female | 12 (31) | 14 (27) |
Ethnicity, n (%)
| ||
Malay | 13 (33) | 8 (15) |
Chinese | 25 (64) | 34 (66) |
Indian | 1 (3) | 8 (15) |
Others | 0 (0) | 2 (4) |
Drug Medication, n (%)
| ||
No Medication | 4 (10) | 2 (4) |
Levadopa only | 15 (39) | 15 (29) |
Dopamine agonist only | 6 (15) | 7 (13) |
Levadopa + Dopamine agonist | 14 (36) | 28 (54) |
Dosage of Levadopa
| ||
Mean ± SE | 172.79 ± 26.89 | 345.98 ± 41.53 |
Median | 150.00 | 150.00 |
Range | 0.00 - 675.00 | 0.00 - 675.00 |
Dosage of DA
| ||
Mean ± SE | 1.05 ± 0.19 | 82.79 ± 12.16 |
Median | 1.00 | 80.00 |
Range | 0.00 - 5.00 | 0.00 - 360.00 |
Diagnosis, n (%)
| ||
One repetitive behaviour | 0 (0) | 30 (57) |
>1 repetitive behaviour | 1 (3) | 15 (29) |
Compulsive medication | 1 (3) | 2 (4) |
>1 repetitive behaviour + Compulsive medication | 0 (0) | 5 (10) |
No repetitive behaviour + Compulsive medication | 37 (94) | 0 (0) |
High resolution melt analyses
Genotype distribution in Parkinson’s disease–impulse control disorder patients
SNP
|
Allele frequency
|
Genotype frequency
| p
-value
| ||||
---|---|---|---|---|---|---|---|
Wild type
|
Heterozygote
|
Mutant
| |||||
DRD1
rs4532
| Control | C (0.06) | T (0.94) | CC (0.02) | TC (0.07) | TT (0.90) | 0.26 |
Case | C (0.24) | T (0.76) | CC (0.06) | TC (0.37) | TT (0.57) | ||
DRD1
rs4867798
| Control | T (0.68) | C (0.32) | TT (0.42) | TC (0.52) | CC (0.06) | 0.35 |
Case | T (0.54) | C (0.46) | TT (0.36) | TC (0.36) | CC (0.28) | ||
DRD1
rs265981
| Control | T (0.18) | C (0.82) | TT (0.03) | TC (0.32) | CC (0.66) | 0.51 |
Case | T (0.21) | C (0.79) | TT (0.02) | TC (0.36) | CC (0.66) | ||
DRD2/ANKK1
rs1800497
| Control | C (0.48) | T (0.52) | TT (0.30) | TC (0.44) | CC (0.26) | 0.27 |
Case | C (0.71) | T (0.29) | TT (0.09) | TC (0.40) | CC (0.51) | ||
DRD3
rs3732783
| Control | T (1.00) | C (0.00) | TT (1.00) | TC (0.00) | CC (0.00) | 0.0014** |
Case | T (0.95) | C (0.05) | TT (0.94) | TC (0.02) | CC (0.04) | ||
DRD3
rs6280
| Control | C (0.24) | T (0.76) | CC (0.05) | TC (0.50) | TT (0.57) | 0.61 |
Case | C (0.33) | T (0.76) | CC (0.08) | TC (0.38) | TT (0.42) | ||
GRIN2B
rs7301328
| Control | G (0.50) | C (0.50) | GG (0.57) | CG (0.38) | CC (0.05) | 0.47 |
Case | G (0.28) | C (0.72) | GG (0.42) | CG (0.50) | CC (0.08) |
DRD1
|
rs4532
|
rs4867798
|
rs265981
|
---|---|---|---|
rs4532
| - | 0.250 | 0.789 |
rs4867798
| - | - | 0.011 |
rs265981
| - | - | - |
DRD3
|
rs3732783
|
rs6280
| |
rs3732783
| - | 0.996 | |
rs6280
| - | - |
Association of DRDs and GRIN2B polymorphisms with Parkinson disease–Impulse control disorder
Model
|
Genotype
|
Control (%)
|
Case (%)
|
OR (95% CI)
|
---|---|---|---|---|
DRD1
rs4532 (C > T)
| ||||
Overdominant
| CC-TT | 35 (94.6) | 32 (61.5) | 1.00 |
TC | 2 (5.4) | 20 (38.5) | 21.33 (1.97-230.64)
**
| |
DRD1
rs4867798 (T > C)
| ||||
Recessive
| TT-TC | 29 (96.7) | 32 (71.1) | 1.00 |
CC | 1 (3.3) | 13 (28.9) | 24.53 (1.68-357.28)
**
| |
DRD2/ANKK1
rs1800497 (C > T)
| ||||
Log-additive
| T- | - | - | 3.77 (1.38-10.30)
**
|
GRIN2B
rs7301328 (G > C)
| ||||
Recessive
| GG-CG | 24 (82.8) | 20 (47.6) | 1.00 |
CC | 5 (17.2) | 22 (52.4) | 25.07 (1.30-483.41)
**
|