Table 2.
Summary of PK gene variants and their associated phenotypes.
| Gene Variant(s) |
Allele/ Genotype |
Association | Study size |
p-value | Reference |
|---|---|---|---|---|---|
| ABCB1 rs1045642 | AA | increased plasma clozapine | 75 | 0.046 | 19593168 |
| ABCB1 rs1045642 | AA | increased risk of Agranulocytosis and Neutropenia with clozapine |
310 | 0.05 | 27168101 |
| ABCB1 rs1045642 | AG+GG | increased weight gain and risk for hypertension with clozapine in men |
65 | 0.026 0.006 |
28919802 |
| ABCB1 rs7787082 | G | nonresponse | 93 | 0.036 | 22722500 |
| ABCB1 rs10248420 | A | nonresponse | 89 | 0.046 | 22722500 |
| ABCC1 rs212090T | AT+TT | increased weight gain and risk for hypertension in men |
65 | 0.022 0.031 |
28919802 |
| ABCG2 rs2231142 | GT+TT | increased dose-adjusted trough concentrations of clozapine |
45 | 0.01 | 27932669 |
| CYP1A2 rs762551 (*1F) |
AA | decreased likelihood of Metabolic Syndrome in non-smokers |
38 | Not given |
27681143 |
| CYP1A2 rs762551 (*1F) |
AA | Increased likelihood of Metabolic Syndrome in smokers |
21 | 0.0213 | 27681143 |
| CYP1A2 rs762551 (*1F) |
AA | nonresponse | 4 | Not given |
15206669 |
| CYP1A2 rs35694136 and/or rs2069514 (*1C) |
DEL/A | increased likelihood of elevated insulin levels |
17 | 0.04 | 17503978 |
| CYP1A2 *1F | *1F/*1F | increased risk of seizures | 108 | 0.033 | 23601795 |
| CYP1A2 *1C | *1C | increased severity of Confusion, Drug Toxicity, Headache, Muscle Rigidity, sedation and Tachycardia |
5 | Not given |
21481946 |
| CYP2C19 | *17/*17 | higher serum N-desmethylclozapine, lower prevalence of diabetes, increased improvement of Schizophrenia symptoms |
17 45 125 |
0.049 0.042 0.012 |
28664816 |
| CYP2C19 | *2/*2 | higher serum clozapine | 75 | 0.036 | 19593168 |
| CYP2C19 | *2 | Increased likelihood of metabolic syndrome |
59 | 0.033 | 27681143 |
| CYP3A5 | *1/*3 | decreased concentrations of clozapine compared to *3/*3 |
92 | < 0.0001 | 28340122 |
| CYP3A43 rs680055 | CG | increased response compared to CC | 152 | 0.013 | 25150845 |
All alleles/genotypes stated as on plus chromosomal strand. The ABCB1 gene is on the minus strand therefore alleles may be shown complementary to in other publications.