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 4 annotations for this variant. Register or sign in to see them.
There are 5 disease-related annotations for this variant. Register or sign in to see them.
VIP Variant in DRD2
It has been reported that the 957C>T polymorphism of DRD2 is associated with both schizophrenia susceptibility substance addiction and treatment. This variant is a synonymous coding SNP located in exon 7. The minor allele (T) frequency varies among geographic groups ranging from 3-8% in African and Asian populations to over 50% in Caucasian populations (see dbSNP for rs6277).
Lawford et al. conducted a study that examined the effect of the 957C>T polymorphism on mRNA levels of DRD2 [Article:15567074]. The authors found that the T allele led to a decrease in mRNA levels and stability whereas the C allele was not found to be associated with any mRNA changes, which led to a relative increase in the expression of DRD2 in carriers of the C allele [Article:15567074]. Results of an in vivo study with (11C)raclopride indicated that the variant increased binding potential by decreasing DRD2 KD (C/C>C/T>T/T), while Bmax was not significantly altered [Article:19582781]. The 957C>T polymorphism is implicated in schizophrenia susceptibility. Several studies have postulated a protective role against schizophrenia for the minor T allele [Articles:16973280, 17087792, 18583979, 19158809]. Shen et al. studied the effect of DRD2 variation (-141C Ins/Del, Ser311Cys, 957C>T, and Taq1A) on aripiprazole response in schizophrenic patients with use of the positive and negative syndrome scale (PANSS) for assessment of drug efficacy [Article:18926547]. The effect of 957C>T polymorphism on PANSS performance was an association of poor aripiprazole response with C/C genotype compared with T/T genotype for excitement symptoms [Article:18926547]. The 957C>T SNP was also investigated in association with substance addiction and treatment. Lerman et al. reported that smokers homozygous for the 957C>T T allele exhibited a better response to NRT [Article:16123753]. Carriers of the wild-type C allele had a higher likelihood of not responding to methadone substitution therapy [Article:18687376]. Recent studies also found that the 957C>T polymorphism in DRD2 was related to learning differences associated with the risk of developing psychiatric disorders in individuals that are carriers of the homozygous CC genotype [Article:19900188].
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.
| Key Publications: | |
|---|---|
| Drugs / Other Molecules | |
| Diseases | Schizophrenia 2 Tobacco Use Disorder 3 |
Appendix
DRD2: C957T
| Genomic Variant & GenBank ID: | 16845875 G>A on NT_033899.7 |
|---|---|
| mRNA Variant & GenBank ID: | 1122 C>T on NM_000795 1035 C>T on NM_016574 |
| Protein Variant & GenBank ID: | 319 Pro 319 >Pro on NP_000786 (long isoform) 290 Pro 290 >Pro on NP_057658 (short isoform) |
| gp Position | chr11:112788669(hg18) |
Connected Diseases
| Evidence | Disease |
|---|---|
| Alcoholism | |
| Schizophrenia | |
| Substance-Related Disorders | |
| Tobacco Use Disorder |
Publications related to rs6277 at chr11:113283459: 6
Cross-References
- UCSC Golden Path:
- chr11:113283459
- dbSNP:
- rs6277
- HapMap:
- rs6277
Platform Availability
- Illumina