Table 1. Published studies of genetic polymorphisms and in vivo D2 receptor BP.
| Study | No. of subjects | Age, years, mean (s.d.) | Sex (% female) | Imaging technique | Reported effects on striatal D2 receptor BP in vivo |
|---|---|---|---|---|---|
| ANKK1 rs1800497 Glu713Lys ‘Taq1A' (missense) | |||||
| Laruelle et al.5 | 47 23a | NA | 14 | [123I] IBZM SPECT | No significant difference between genotype groups; no significant difference between healthy and schizophrenic participants |
| Pohjalainen et al.6 | 54 | 40 (17) | 39 | [11C] RAC PET | A1 carriers significantly lower than A2/A2 |
| Jönsson et al.4 | 56 | 32 (12) | 23 | [11C] RAC PET | A1 carriers significantly lower than A2/A2 |
| Brody et al.12 | 45 | 37 (11) | 29 | [11C] RAC PET | No significant difference between genotype groups; no significant association with cigarette-induced decrease in binding |
| Hirvonen et al.10 | 45 | 36 (14) | 40 | [11C] RAC PET | A1 carriers significantly lower than A2/A2; subsample of Pohjalainen et al.6 |
| Hirvonen et al.18 | 38 | 29 (7) | 0 | [11C] FLB 457 PET | A1 carriers significantly higher than A2/A2 in cerebral cortex and thalamus (extrastriatal) |
| Savitz et al.11 | 24 12b | 35 (8) 38 (11)b | 54 67b | [11C] RAC PET | A1 carriers significantly lower than A2/A2 among healthy controls; A1 carriers significantly higher than A2/A2 among depressed patients; no significant association with reward-related decrease in binding |
| Wagner et al.13 | 13 12c | ~30 ~33 | 0 | [11C] RAC PET | No significant difference between genotype groups for either healthy controls or patients with traumatic brain injury |
| COMT rs4680 Val158Met (missense) | |||||
| Brody et al.12 | 45 | 37 (11) | 29 | [11C] RAC PET | No significant difference between genotype groups for baseline binding; significantly greater cigarette-induced decrease in binding among Val/Val subjects relative to Met carriers |
| Hirvonen et al.19 | 45 | 36 (14) | 40 | [11C] RAC PET | No significant difference between genotype groups |
| Hirvonen et al.19 | 38 | 29 (7) | 0 | [11C] FLB 457 PET | No significant difference between genotype groups (extrastriatal) |
| Boot et al.20 | 15d | NA | 60d | [123I] IBZM SPECT | Met hemizygotes significantly lower than Val hemizygotes (all participants with 22q11 deletion syndrome) |
| DAT (SLC6A3) 40-bp VNTR polymorphism (3′ untranslated region) | |||||
| Brody et al.12 | 45 | 37 (11) | 29 | [11C] RAC PET | No significant difference between genotype groups for baseline binding; significantly greater cigarette-induced decrease in binding among 9-repeat allele carriers compared with 10-repeat homozygotes |
| Wagner et al.13 | 13 12c | NA | 0 | [11C] RAC PET | No significant difference between genotype groups in healthy controls; 10-repeat homozygotes marginally higher than 9-repeat carriers among patients with traumatic brain injury |
| DRD2 rs1079597e ‘Taq1B' (intronic) | |||||
| Laruelle et al.5 | 47 23a | NA | 14 | [123I] IBZM SPECT | No significant difference between genotype groups; no significant difference between healthy and schizophrenic participants |
| Jönsson et al.4 | 56 | 32 (12) | 23 | [11C] RAC PET | B1 carriers significantly lower than B2/B2 |
| DRD2 rs1076560e G>T (intronic) | |||||
| Bertolino et al.21 | 32 | NA | NA | [123I] IBZM SPECT | T-allele carriers significantly lower than G/G; binding values not reported |
| Taurisano et al.22 | 26 | 23 (3) | 50 | [123I] IBZM SPECT | Main effect of genotype not reported; significant interaction between genotype and schizotypy; binding values not reported |
| DRD2 rs6277 C957T (synonymous) | |||||
| Hirvonen et al.23, 24 | 45 | 36 (14) | 40 | [11C] RAC PET | T allele associated with significantly higher BP |
| Hirvonen et al.10 | 45 | 36 (14) | 40 | [11C] RAC PET | T allele associated with significantly lower affinity (Kd); no significant association with receptor density (Bmax); subsample of Hirvonen et al.23, 24 |
| Hirvonen et al.18 | 38 | 29 (7) | 0 | [11C] FLB 457 PET | T allele associated with significantly lower BP in cerebral cortex and thalamus (extrastriatal) |
| DRD2 rs1801028 Ser311Cys (missense) | |||||
| Pohjalainen et al.25 | 49 | 41 (18) | 33 | [11C] RAC PET | No significant difference between genotype groups |
| DRD2 rs1799732 −141C ins/del (upstream) | |||||
| Jönsson et al.4 | 56 | 32 (12) | 23 | [11C] RAC PET | Deletion associated with significantly higher binding |
| Hirvonen et al.18 | 38 | 29 (7) | 0 | [11C] FLB 457 PET | No significant difference between genotype groups (only extrastriatal regions measured) |
| DRD2 (CA)n repeat polymorphism (intron 2) | |||||
| Jönsson et al.4 | 56 | 32 (12) | 23 | [11C] RAC PET | No significant difference between genotype groups |
| DRD2 rs4274224 (intronic) and rs12364283 (upstream) | |||||
| Peciña et al.26 | 52 | 27 (5) | 58 | [11C] RAC PET | No significant difference between genotype groups for baseline binding for either variant; significantly lower pain-induced decrease in binding among rs4274224 A/G heterozygotes relative to A/A or G/G homozygotes |
| DRD3 rs6280 Ser9Gly (missense) | |||||
| Savitz et al.27 | 26 10b | 34 (8) 38 (11)b | 58 80b | [11C] RAC PET | No significant difference between genotype groups for baseline binding; Gly allele associated with significantly greater reward-induced decrease in binding |
| DRD4 48-bp VNTR polymorphism (exon 3) | |||||
| Brody et al.12 | 45 | 37 (11) | 29 | [11C] RAC PET | No significant difference between genotype groups for baseline binding; significantly greater cigarette-induced decrease in binding among subjects with fewer than seven repeats |
| HTR2C rs6318 Cys23Ser (missense) | |||||
| Mickey et al.28 | 54 | 27 (5) | 60 | [11C] RAC PET | No significant difference between genotype groups for baseline binding; significantly greater pain-induced decrease in binding among Ser allele carriers |
| LEP rs12706832 (intronic) and rs3828942 (intronic) | |||||
| Burghardt et al.29 | 50 | 26 (5) | 56 | [11C] RAC PET | No significant difference between genotype groups for baseline binding for either variant; significantly greater pain-induced decrease in binding among rs12706832 G/G homozygotes |
| OPRM1 rs1799971 A118G Asn40Asp (missense) | |||||
| Domino et al.30 | 20f | 26 (5)f | 0f | [11C] RAC PET | Differences between genotype groups not reported for baseline binding; significantly greater cigarette-induced decrease in binding among G-allele carriers relative to A/A homozygotes |
| OXT rs4813625 (upstream) | |||||
| Love et al.31 | 55 | 27 (5) | 58 | [11C] RAC PET | No significant difference between genotype groups for baseline binding; among females only, significantly greater pain-induced decrease in binding among C-allele carriers compared with G/G |
| PER2 VNTR polymorphism (intron 3) | |||||
| Shumay et al.32 | 52 | 35 (9) | 17 | [11C] RAC PET | Carriers of 3-repeat or rare alleles significantly lower than 4-repeat homozygotes |
Abbreviations: BP, binding potential; bp, base pair; FLB 457, (S)-5-bromo-N-((1-ethyl-2-pyrrolidinyl)methyl)-2,3-dimethoxybenzamide; IBZM, iodobenzamide; NA, not available; PET, positron emission tomography; RAC, raclopride; SPECT, single-photon emission computed tomography; VNTR, variable-number tandem repeat.
All data are from healthy adult subjects unless otherwise specified.
a
Participants with schizophrenia.
b
Participants with major depressive disorder.
c
Participants with traumatic brain injury.
d
Participants with 22q11 deletion syndrome.
e
rs1079597 and rs1076560 are in linkage disequilibrium (r2=0.87, D′=0.93, northern and western European ancestry).
f
Participants with tobacco dependence, otherwise healthy.