Important Variant Information for SULT1A1
Submitted by: Michelle Hildebrandt, Araba Adjei, Richard Weinshilboum, and Julie A. Johnson(PPII)
Reviewed by: Zeruesenay Desta, Anne Nguyen, and David Flockhart (COBRA)
Submitted date: January 19, 2007
There are Four Important Variants for SULT1A1.
- SULT1A1: 638 G>A (213Arg>His)(rs9282861)
- SULT1A1: 667A>G (223Val>Met)(rs1801030)
- SULT1A1: -624G>C(rs3760091)
- SULT1A1: -396 G>A(rs750155)
1. SULT1A1: 638G>A (213Arg>His) (rs9282861)
| Gene HGNC Name: | SULT1A1 |
|---|---|
| Variant Summary: | The most common SULT1A1 variant allele found among most populations is 638G>A which 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 [PMID: 11207031]. SULT1A1*2 was associated with lower enzyme activity and resulted in a more thermal labile protein compared to SULT1A1*1(wild-type) in the platelet [PMID: 9345314]. In the liver, SULT1A1*2 resulted in a more thermal labile protein, but was not strongly associated with lower activity [PMID: 10413297]. Substrate kinetic studies of SULT1A1*1 and *2 allozymes showed similar affinities for the probe substrate 4-nitrophenol and cosubstrate PAPS [PMID: 10413297, 10423517]. SULT1A1*2 substrate specificities were comparable to SULT1A1*1 [PMID: 10423517], however SULT1A1*2 was less efficient in the activation of several promutagens [PMID: 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 [PMID: 14520706]. Another study suggested that the *2 variant may act as a risk modifier for breast cancer in postmenopausal women [PMID: 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 [PMID: 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 to controls [PMID: 15093672]. A study into the metabolism of tamoxifen during adjuvant breast cancer treatment showed that SULT1A1*2 was not associated with altered concentrations of tamoxifen or its metabolites [PMID: 15632378]. Contradicting association studies have also been published for prostate cancer [PMID: 14973106, 10959796]. |
| Key PubMed IDs: | 11207031, 9345314, 10413297 |
| 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 |
| dbSNP rs#: | rs9282861 |
| GoldenPath Position: | chr16:28525015 ;(hg18) |
| Key Drugs/Substrates: | Same as wild-type |
| Key Phenotypes/Diseases: | Same as wild-type |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): | PA126721774(Coriell Cell Line GM17102; Coriell DNA: NA17102) |
| DNA Source Containing Heterozygous Reference Allele(Coriell Lines): | PA126721776 (Coriell Cell Line GM17103; Coriell DNA: NA17103) |
| DNA Source Containing Homozygous Minor Allele(Coriell Lines): |
PA126721835 (Coriell Cell Line GM17120; Coriell DNA: NA17120) |
| Phenotype Data Sets | Hot flashes in tamoxifen patients (PA133888879), Lipid measurements in tamoxifen study - set 2 (PA133888980), Patient responses to tamoxifen (PA646603), Thyroid binding globulin in tamoxifen patients (PA133888873). SULT1A1*2 was genotyped in breast cancer patients being treated with tamoxifen to determine if the *2 variant allele was associated with variation in drug response. |
| Key Haplotypes: | SULT1A1: (638G>A, -624G>C and -396A>G) |
2. SULT1A1: 667A>G (223 Val>Met)(rs1801030)
| Gene HGNC Name: | SULT1A1 |
|---|---|
| Variant Summary: | The second most common SULT1A1 SNP is the 667A>G which results in the amino acid substitution 223Met>Val. This variant is commonly known as SULT1A1*3. The SULT1A1*3 genotype has allele frequencies of 0.012, 0.006 and 0.229 in Caucasian, Chinese and African-American subjects respectively [PMID: 11207031]. The affinity to the substrate 4-nitrophenol and the cosubstrate PAPS was increased for COS-1 expressed SULT1A1*3 compared to SULT1A1*1 [PMID: 10413297]. |
| Key PubMed IDs: | 11207031, 10413297 |
| Genomic Variant & GenBank ID: | 19,930,564 C>T on NT_010393.15 |
| mRNA Variant & GenBank ID: | 777 G>A on NM_001055.2 (This reference sequence has the variant allele.) |
| Protein Variant & GenBank ID: | 223 Val>Met on NP_001046.2(This reference sequence has the variant allele.) |
| dbSNP rs#: | rs1801030 |
| GoldenPath Position: | chr16:28524986 ;(hg18) |
| Key Drugs/Substrates: | Same as wild-type |
| Key Phenotypes/Diseases: | Same as wild-type |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): |
PA126721774(Coriell Cell Line GM17102; Coriell DNA: NA17102) |
| DNA Source Containing Heterozygous Reference Allele (Coriell Lines): |
PA126721803 (Coriell Cell Line GM17112; Coriell DNA: NA17112) |
3. SULT1A1: -624G>C(rs3760091)
| Gene HGNC Name: | SULT1A1 |
|---|---|
| Variant Summary: | Several SNPs were identified in the SULT1A1 5'-flanking region including a G>C change at -624 which creates a putative Sp1 binding site [PMID: 15970794]. This variant is present at allele frequencies greater than 30% for Caucasian, African-American and Chinese subjects and shows high linkage disequilibrium with SULT1A1*2. Functional studies showed that promoter haplotypes including the -624G>C variant were predictors of SULT1A1 activity in the platelet with the C allele being associated with increased SULT1A1 activity [PMID: 15970794]. |
| Key PubMed IDs: | 15970794 |
| Genomic Variant & GenBank ID: | 19,933,879 C>G on NT_010393.15 |
| mRNA Variant & GenBank ID: | none |
| Protein Variant & GenBank ID: |
NA |
| dbSNP rs#: | rs3760091 |
| GoldenPath Position: | chr16:28528301 (hg18) |
| Key Drugs/Substrates: | Same as wild-type |
| Key Phenotypes/Diseases: |
Same as wild-type |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): |
PA126721835(Coriell Cell Line GM17120; Coriell DNA: NA17120) |
| DNA Source Containing Heterozygous Reference Allele(Coriell Lines): |
PA126721774(Coriell Cell Line GM17102; Coriell DNA: NA17102) |
| DNA Source Containing Homozygous Minor Allele (Coriell Lines): |
PA126721804 (Coriell Cell Line GM17113; Coriell DNA: NA17113) |
| Key Haplotypes: | SULT1A1: (638G>A, -624G>C and -396A>G) |
4. SULT1A1: -396 G>A(rs750155)
| Gene HGNC Name: | SULT1A1 |
|---|---|
| Variant Summary: | Sequence analysis of the SULT1A1 promoter region identified a SNP at location -396 resulting in a G>A change [PMID: 15970794]. This variant was found at allele frequencies of 0.48, 0.63 and 0.42 in Caucasian, African-American and Chinese subjects, respectively. This location is in linkage disequilbrium with SULT1A1*2. Presence of -396A was associated with decreased SULT1A1 activity for African-Americans and increased activity for Caucasians [PMID: 15970794]. |
| Key PubMed IDs: | 15970794 |
| Genomic Variant & GenBank ID: | 19,933,651 C>T on NT_010393.15 |
| mRNA Variant & GenBank ID: | 78G>A on NM_177534.1 |
| Protein Variant & GenBank ID: |
NA |
| dbSNP rs#: | rs750155 |
| GoldenPath Position: | chr16:28528073 ;(hg18) |
| Key Drugs/Substrates: | Same as wild-type |
| Key Phenotypes/Diseases: |
Same as wild-type |
| DNA Source Containing Homozygous Reference Allele(Coriell Lines): |
PA126721774(Coriell Cell Line GM17102; Coriell DNA: NA17102) |
| DNA Source Containing Heterozygous Reference Allele(Coriell Lines): |
PA126721776 (Coriell Cell Line GM17103; Coriell DNA: NA17103) |
| DNA Source Containing Homozygous Minor Allele(Coriell Lines): |
PA126721835 (Coriell Cell Line GM17120; Coriell DNA: NA17120) |
| Key Haplotypes: | SULT1A1: (638G>A, -624G>C and -396A>G) |