Clinical Annotations
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Variant Annotations
PharmGKB variant annotations provide information about variant-drug pairs based on individual PubMed publications. Each annotation represents information from a single paper and the goal is to report the information that the author states, not an interpretation of the paper. The PMID for supporting PubMed publications is found in the "Evidence" field.
Information presented, including study size, allele frequencies and statistics is taken directly from the publication. However, if the author does not correct p-values in cases of multiple hypotheses, curators may apply a Bonferroni correction. Curators attempt to report study size based on the actual number of participants used for the calculation of the association statistics, so the number may vary slightly from what is reported in the abstract of the paper. OMB Race Category information is derived from the paper and mapped to standardized categories. Category definitions may be found by clicking on the "OMB Race Category" link.
There are 15 annotations for this variant. Register or sign in to see them.
There are 12 disease-related annotations for this variant. Register or sign in to see them.
VIP Variant in DRD2
The -141C Ins/Del polymorphism of DRD2 has been reported to influence the outcome of both antipsychotic [Article:20194480] and addiction treatments [Articles:11920858, 16123753]. The -141C Ins/Del (rs1799732) polymorphism is located in the promoter region of the DRD2 gene and is found at an allele frequency of about 22% of the Japanese population. This allele is less common among Chinese and Caucasian populations (9%) [Article:9713903]. Allele frequencies are known for a number of different populations, and of these, the deletion polymorphism is the most common allele in only the Yoruban sample set see The ALlele FREquency Database.
A number of studies have shown that the -141C Ins/Del polymorphism of DRD2 appears to have a role in determining the response to antipsychotic drugs in schizophrenic patients, in which the Ins allele is associated with favorable treatment outcome (see Table1). But there are also contrary results reporting no association (Table1). A recent meta-analysis examined the relationship of DRD2 genetic variation and clinical response to antipsychotic treatment (risperidone, olanzapine, chlorpromazine, clozapine, and aripiprazole) [Article:20194480]. This analysis included six studies, which met the inclusion criteria for reported results on the -141C Ins/Del polymorphism, with a total sample size of 687 patients [Article:20194480]. The authors showed that the group of Del allele carrier was significantly associated with poorer antipsychotic drug response relative to the Ins/Ins genotype [Article:20194480]. The -141C Ins/Del variant has also been investigated in the context of substance addiction and treatments. Li and colleagues found a positive association between nasal inhaled but not injected heroin use and the -141C Ins/Del DRD2 polymorphism in Chinese subjects [Article:11920858]. Lerman et al. suggest that the -141C Ins/Del polymorphism may influence whether bupropion or nicotine replacement therapy (NRT) would be more effective for tobacco dependence treatment [Article:16123753]. The authors found that bupropion was more effective for patients who were homozygous for the Ins allele, whereas NRT appeared to be more helpful for patients who were homozygous for the Del allele [Article:16123753].
Note: The DRD2 gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand, therefore the alleles within our variant annotations will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.
Table: Effect of the -141C Ins/Del polymorphism on antipsychotics response in schizophrenic patients based on studies investigating association between DRD2 variants and response to antipsychotic drugs.
| Subjects (population) | Antipsychotic drug | Treatment Duration | Response measurement | Genotyped DRD2 polymorphisms | -141C Ins/Del effect | Reference |
|---|---|---|---|---|---|---|
| 151 schizophrenics 95 controls (Caucasian) | clozapine | - | GAS | -141C Ins/Del | No association | [Article:991813] |
| 170 schizophrenics; 121 controls (Japanese) | antipsychotic drugs not specified | - | PANSS | -141C Ins/Del | No association | [Article:9858029] |
| 49 schizophrenic inpatients (Japanese) | bromperidol or nemonapride | 3 weeks | BPRS | -141C Ins/Del | Ins allele associated with greater improvement (only for anxiety-depression symptoms) | [Article:11505224] |
| 73 schizophrenic patients (Japanese) | risperidone | 8 weeks | PANSS | -141C Ins/Del; Taq1A | Ins-A2/Del-A1 diplotype associated with better response | [Article:14610521] |
| 135 schizophrenic inpatients (Chinese) | chlorpromazine | 8 weeks | BPRS | Del - | genotype associated with higher degree of improvement | [Article:15694263] |
| DSM-III-R or DSM-IV schizophrenics (183 Caucasian; 49 African-American) | clozapine | 6 months | BPRS | -141C Ins/Del; Taq1A; Taq1B; and rs1125394 | no association | [Article:15830237] |
| 61 first-episode schizophrenia patients (41% African American; 28% Caucasian; 18% Hispanic; 5% Asian; 8% other) | olanzapine or risperidone | 16 weeks | CGIIS | -141C Ins/Del; A-241G | -141C Del allele showed significantly longer time to respond relative to Ins/Ins homozygotes | [Article:16513877] |
| 125 schizophrenia patients (Chinese) | risperidone | 8 weeks | BPRS | -141C Ins/Del; Taq1B; rs1076562; Taq1A | no association | [Article:17105675] |
| 128 schizophrenic inpatients (Han Chinese) | aripiprazole | 4 weeks | PANSS | -141C Ins/Del; Taq1A; C957T; Ser311Cys | no significant effect | [Article:18926547] |
BPRS: Brief Psychiatric Rating Scale; CGIIS: Clinical Global Impression Improvement Scale; GAS: Global Assessment Scale; PANSS: Positive and Negative Symptom Scale;
-141C Ins/Del (rs1799732); Taq1A (rs1800497); Taq1B (rs1079597); -241A>G (rs1799978); 957C>T (rs6277); Ser311Cys (rs1801028)
| Key Publications: | |
|---|---|
| Drugs / Other Molecules |
Drug (5)
|
| Diseases | Schizophrenia 6 7 Tobacco Use Disorder 8 |
Appendix
DRD2: \-141C Ins/Del
| Genomic Variant & GenBank ID: | 16833244 G>A on NT_033899.7 |
|---|---|
| mRNA Variant & GenBank ID: | There are no changes to the DRD2 mRNA, but this variation causes a change in the ANKK1 mRNA |
| Protein Variant & GenBank ID: | There are no changes to the DRD2 protein, but this variation causes a nonsynonymous change in ANKK1. |
| dbSNP rs#: | [rs1800497] |
| GoldenPath Position: | chr11:112776038 (hg18) |
Connected Drugs
| Evidence | Drug |
|---|---|
| aripiprazole | |
| Bromperidol | |
| bupropion | |
| chlorpromazine | |
| clozapine | |
| heroin | |
| nemonapride | |
| nicotine | |
| olanzapine | |
| risperidone |
Connected Drug Classes
| Evidence | Drug Class |
|---|---|
| Clinical Annotation, Variant Annotation | antipsychotics |
Connected Diseases
| Evidence | Disease |
|---|---|
| Alcoholism | |
| Schizophrenia | |
| Tobacco Use Disorder |
Publications related to rs1799732 at chr11:113346252: 16
Cross-References
- UCSC Golden Path:
- chr11:113346252
- dbSNP:
- rs1799732
- ALFRED:
- SI000135J