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.
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VIP Variant in DRD2
It is not clear whether the Ser311Cys polymorphism is associated with schizophrenia. There have been reports both supporting and refuting such results. This variant is a C>G SNP in exon 7 that alters the codon 311 from the more common Ser to the less common Cys. The Cys311 variant has decreased affinity for dopamine [Article:8824240]. The minor allele frequency (G allele) is 0.02 based on the 102 individuals of self-described heritage (African/African American, n=24, Caucasian, n=31, Hispanic, n=23, and Pacific Rim, n=24) see dbSNP. From the same data set, the frequency of the G allele is higher in a self-described Pacific Rim population (0.043) than that in a Caucasian population (0.016).
There is published evidence both supporting [Articles:7907680, 7909081, 8723039, 11011590, 12707934, 16402354] and refuting [Article:9650635] the association between Ser311Cys polymorphism of the DRD2 gene and schizophrenia. A possible link between the Cys allele of 311 Ser>Cys in DRD2 and schizophrenia was first reported in the mid 1990s [Articles:7907680, 7909081, 8723039], although Goldman et al. found no correlation between carriers of Cys 311 and schizophrenia in a Native American population [Article:9650635]. Jonsson et al. examined the possible association of Ser311Cys and schizophrenia in control and schizophrenic populations, both of Swedish origin [Article:12707934]. The schizophrenic patient population (n = 173) showed a higher allele frequency of Cys 311 than the control population (n = 236) [Article:12707934]. Interestingly, this association was detected only in male patients [Article:12707934]. In a more recent study by Glatt and Jonsson [Article:16402354], an analysis was conducted of several different studies which contained a total of 3,707 schizophrenia patients and 5,363 control subjects. The authors found that the Cys 311 allele had a significant effect [Article:16402354]. In the same study, the authors reported that Cys/Ser heterzygotes were at increased risk for schizophrenia as compared to the Ser/Ser homozygotes, but there was no increased risk detected for Cys/Cys homozygotes [Article:16402354].
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: | |
|---|---|
| Diseases | Schizophrenia 1 2 3 |
Appendix
DRD2: Ser311Cys
| Genomic Variant & GenBank ID: | 16845900 G>C on NT_033899.7 |
|---|---|
| mRNA Variant & GenBank ID: | 1097 C>G on NM_000795.2 1010 C>G on NM_016574.2 |
| Protein Variant & GenBank ID: | 311 Ser> Cys on NP_000786 (long isoform) 282 Ser>Cys on NP_057658 (short isoform) |
| gp Position | chr:112788694(hg18) |
Publications related to rs1801028 at chr11:113283484: 5
Cross-References
- UCSC Golden Path:
- chr11:113283484
- dbSNP:
- rs1801028
- ALFRED:
- SI000138M