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 13 annotations for this variant. Register or sign in to see them.
VIP Variant in SULT1A1
Note: The SULT1A1 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 and haplotypes may differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.
The most common SULT1A1 variant allele found among most populations is 638G>A, where position 1 corresponds to the A of the ATG protein translation start codon. This SNP results in the amino acid substitution 213Arg>His. This variant is commonly known as SULT1A1*2. The SULT1A1*2 genotype has allele frequencies of 0.332, 0.080 and 0.294 in Caucasian, Chinese and African-American subjects, respectively [Article:11207031].
SULT1A1*2 was associated with lower enzyme activity and resulted in a more thermolabile protein compared with SULT1A1*1(wild-type) in the platelet [Article:9345314]. In the liver, SULT1A1*2 resulted in a more thermolabile protein, but it was not strongly associated with lower activity [Article:10413297]. Substrate kinetic studies of SULT1A1*1 and *2 allozymes showed similar affinities for the probe substrate 4-nitrophenol and cosubstrate PAPS [Articles:10413297, 10423517]. SULT1A1*2 substrate specificities were comparable to SULT1A1*1 [Article:10423517], however SULT1A1*2 was less efficient in the activation of several promutagens [Article:11535246].
Numerous pharmacogenetic studies of SULT1A1*2 in relationship to estrogen metabolism and hormone-dependent cancers have been reported. These studies have had varying results linking the SULT1A1*2 variant allele with risk of cancer or response to therapy. SULT1A1*2 was not shown to be associated with breast cancer in a French population, except in smokers where it increased the risk of breast cancer [Article:14520706]. Another study suggested that the *2 variant may act as a risk modifier for breast cancer in postmenopausal women [Article:16141802]. Furthermore, SULT1A1*2 has been found to be associated with lymph node metastasis in breast cancer patients while not being a direct risk factor for breast cancer [Article:15377847]. In contrast, a case-control study of Chinese woman found that the SULT1A1*2 allele was present at a higher frequency in breast cancer patients compared with controls [Article:15093672]. A study of the metabolism of tamoxifen during adjuvant breast cancer treatment showed that SULT1A1*2 was not associated with altered concentrations of tamoxifen or its metabolites [Article:15632378]. Contradicting association studies have also been published for prostate cancer [Articles:14973106, 10959796, 18368507]. A recent meta-analysis concluded that the SULT1A1*2 polymorphism was protective in genitourinary cancers, but was associated with increased upper aerodigestive tract cancers [Article:18854828].
| Key Publications: | |
|---|---|
| Drugs / Other Molecules | |
| Diseases | Breast Neoplasms 14 15 16 17 Colorectal Neoplasms 18 Esophageal Neoplasms 19 Prostatic Neoplasms 20 21 |
| Phenotype Datasets |
Hot flashes in tamoxifen patients Lipid measurements in tamoxifen study - set 2 Patient responses to tamoxifen Thyroid binding globulin in tamoxifen patients |
Appendix
1. SULT1A1: 638G>A (213Arg>His) *(rs9282861) (SULT1A1*2)*
| Genomic Variant & GenBank ID: | 19,930,593 C>T on NT_010393.15 |
|---|---|
| mRNA Variant & GenBank ID: | 748G>A on NM_001055.2 |
| Protein Variant & GenBank ID: | 213Arg>His on NP_001046.2 |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): | |
| PA126721774@pgkb](Coriell Cell Line GM17102; Coriell DNA: NA17102) | |
| DNA Source Containing Heterozygous Reference Allele(Coriell Lines): | |
| PA126721776@pgkb] (Coriell Cell Line GM17103; Coriell DNA: NA17103) | |
| DNA Source Containing Homozygous Minor | |
| | |
| PA126721835@pgkb] (Coriell Cell Line GM17120; Coriell DNA: NA17120) | |
| Key Haplotypes: | SULT1A1: (638G>A, -624G>C and -396A>G) |
| gp position | chr16:28525015(hg18) |
Connected Drugs
| Evidence | Drug |
|---|---|
| acetaminophen | |
| conjugated estrogens | |
| minoxidil | |
| tamoxifen |
Connected Drug Classes
| Evidence | Drug Class |
|---|---|
| VIP Annotation | estrogens |