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Shad. J Transl Genet Genom 2023;7:141-65 https://dx.doi.org/10.20517/jtgg.2023.11 Page 149

-DRD1 rs4532 and DRD3 rs4532 and DRD3 rs1394016 for BPOS change (P
rs1394016 = 0.028).
In African Americans -In African Americans, positive interactions
- DRD2 C957T and DRD3 observed between DRD2 C957T and DRD3
Ser9Gly Ser9Gly for BPRS change (corrected P = 0.039);
-DRD1 rs686 and DRD2 Taq DRD1 rs686 and DRD2 TaqIA for BPOS % change
IA (corrected P = 0.033); and DRD1 rs265976 and
-DRD1 rs265976 and GRIN2A (corrected P = 0.005) for BNEG %
GRIN2A change

Bosia et al., -COMT Val158Met 107 Italian 217-248 mg/day 8 and 16 weeks PANSS - COMT Met allele and 5-HT1A-R C allele
[83]
2015 (rs4680) and HTR1A- predicted a better CLZ response than COMT
1019C/G (rs6295) Val/Val and 5-HT1A-R C allele (P = 0.01) and
COMT Val/Val and 5-HT1A-R G/G
(P = 0.04)
Rajagopal et al., -DRD4 120 bp duplication 93 Indian Average dose 320 mg/day At least 12- BPRS COMT Met carriers (Met/Met or Val/Met) and
[84]
2018 and in responders and 387 in weeks 120-bp allele carriers (120/120 or 120/240)
-COMT Val158Met nonresponders showed a better CLZ response than those
without these alleles (0.003)

5HT: 5 Hydroxytryptamine; ACTT: auditory consonant trigram test; BNEG: BPRS subscale for negative symptoms; bp: base pair; BPOS: BPRS subscale for positive symptoms; BPRS: brief psychiatric rating scale; CGI-I:
clinical global impression improvement; CIA: clozapine-induced agranulocytosis; CIGT: category instance generation test; COMT: catechol-O-methyl transferase; COWA: controlled oral word association test; CYP:
cytochrome P450; DRD1: gene for dopamine receptor-1; DRD2: gene for dopamine receptor-2; DRD3: gene for dopamine receptor-3; DRD4: gene for dopamine receptor-4; DSST: digit symbol substitution test; HLA:
human leukocyte antigen; HTR1A: gene for serotonin receptor-1A; HTR2A: gene for serotonin receptor-2A; HTR2A: gene for serotonin receptor-2A; HTR3A: gene for serotonin receptor-3A; HTR6: gene for serotonin
receptor-6; OR: odds ratio; PANSS: positive and negative syndrome scale; SLC6A3: gene for dopamine transporter; SLC6A4: gene for serotonin transporter.

found the T allele of the T102C polymorphism [75,86] , two reported HTR2A His452Tyr (rs6314) to be associated with good clozapine response [72,74] , and one

[73]
found the G-1438A SNP as a significant predictor for clozapine response . The HTR3A gene showed significant results in two studies [76,77] . The significant
[78]
change in clozapine response with the SLC6A4 gene for the serotonin transporter was also reported in one study . One study produced significant results in
clozapine response with HTR6 and one with HTR2C . In addition, four studies used more than one candidate gene to conduct a combinatorial analysis to
[79]
[80]
report predictability in clozapine response [81-84] . Three GWAS studies were not included in the 32 formally reviewed studies but have been discussed in the
"DISCUSSION" Section [62,87,88] .

Like the genetic predictability for CIA, genetic predictors for clozapine response require significantly more research. This is despite replicated findings with

some of the pharmacokinetic and pharmacodynamic genetic predictors for clozapine response, including those from the combinatorial assays. Like the genetic
predictability of CIA, the genetic predictors of clozapine efficacy are also compromised by the small sample sizes, controversial findings, and lack of large
genome-wide studies.