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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There are 2 disease-related annotations for this variant. Register or sign in to see them.
VIP Variant in PTGS2
The 8473T>C variant is located in the 3'UTR where it may stabilize the mRNA 19930591. CC individuals were shown to have lower PTGS2 expression than TT individuals, with CT individuals having intermediate expression [Article:16678543]. It has also been discussed in the literature as 6498T>C [Article:16678543].
The C variant occurs at a frequency of 0.355 in Caucasians, 0.435 in Native American/Hispanic and 0.667 in African/African American sample sets in the SNP500Cancer control sample set from the Coriell collection [Article:16381944]. The C variant was also observed at a frequency of 0.291 in German Caucasians [Article:18085997].
Several studies have associated this variant with risk for cancer (see table 2 in Skarke et al [Article:18085997]) including basal cell carcinoma, breast cancer, lung cancer, bile duct cancer and colorectal cancer although there are contradictory reports for lung cancer and breast cancer and no association was reported for cervical cancer. One study has reported association between diet and this variant and disease risk. High salmon-type fish consumers with the C-allele had a 72% lower risk of prostate cancer compared to those eating low or no fish [Article:17066444].
In a study of Chinese children, carriers of the C allele had a higher risk of developing asthma than those homozygous for the T allele [Article:17573729].
There are conflicting reports concerning the impact of this variant for cardiovascular disease. The 8743T allele was associated with decreased risk ratio of Acute Coronary Syndrome (ACS) in Polish CAD patients (in combination with rs708494 in PTGER2) [Article:18989535]. Danish male C variant carriers of 8473T>C were at lower risk of ACS (IRR=0.75, CI=0.61-0.93, p=0.008) than TT homozygotes, and this was independent of NSAID use [Article:19748095].
Homozygous TT genotype was associated with better progression free survival and overall survival in patients with advanced colorectal cancer treated with XELOX (capecitabine and oxaliplatin) chemotherapy [Article:19219602].
Also the TT genotype was associated with lower risk for severe pain in lung cancer patients [Article:19773451]. This may have relevance for pain response to NSAIDs although literature searches did not find data to support this. Lee et al, measured this SNP in a study of rofecoxib vs ibuprofen pain relief, however no interaction was discussed for this particular variant [Article:16678543].
Note: The PTGS2 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 | Acute coronary syndrome Asthma Bile Duct Neoplasms Breast Neoplasms Carcinoma, Basal Cell Cardiovascular Diseases Colorectal Neoplasms Lung Neoplasms Pain Prostatic Neoplasms |
Appendix
2. PTGS2:8473T>C (rs5275)
| Genomic Variant & GenBank ID: | 8494T>C on AY382629.1 |
|---|---|
| mRNA Variant & GenBank ID: | 2379T>C on NM_000963.2 |
| Protein Variant & GenBank ID: | NA |
| GoldenPath Position: | chr1:184909681 (hg18) |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): | NA12146 |
| DNA Source Containing Heterozygous Reference Allele(Coriell Lines): | NA07000 |
| DNA Source Containing Homozygous Minor Allele(Coriell Lines): | NA12144 |
Connected Drugs
| Evidence | Drug |
|---|---|
| capecitabine | |
| oxaliplatin |
Connected Drug Classes
| Evidence | Drug Class |
|---|---|
| VIP Annotation | Antiinflammatory agents, non-steroids |
Connected Diseases
Publications related to rs5275 at chr1:186643058: 8
Cross-References
- UCSC Golden Path:
- chr1:186643058
- dbSNP:
- rs5275
- ALFRED:
- SI458556H
- HapMap:
- rs5275
- Seattle SNP:
- PTGS2-008494
Platform Availability
- Illumina