Rs34815109

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Merged intors3064744
Orientationplus
is asnp
is mentioned by
dbSNPrs34815109
PheGenIrs34815109
nextbiors34815109
hapmaprs34815109
1000 genomesrs34815109
hgdprs34815109
ensemblrs34815109
gopubmedrs34815109
geneviewrs34815109
scholarrs34815109
googlers34815109
pharmgkbrs34815109
gwascentralrs34815109
openSNPrs34815109
23andMers34815109
23andMe allrs34815109
SNP Nexus

SNPshotrs34815109
SNPdbers34815109
MSV3drs34815109
StatusMerged into rs3064744
GeneUGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10
Chromosome2
Orientationplus
Position234668880
ReferenceGRCh37.p2 37.2/134
Max Magnitude
Geno Mag Summary
(-;-) normal
(-;TA) some effects of higher bilirubin
(TA;TA) effects of higher bilirubin; irinotecan toxicity; tranilast toxicity
Make rs34815109(-;ATAT)
Make rs34815109(ATAT;ATAT)
Although the insertion is supposed to be the minor allele, the majority of FTDNA v2 and 23andMe v2 results show II as the result, so use caution when interpreting this result.

rs34815109 is one of four SNPs all describing an insertion/deletion polymorphism in the promoter region of the UGT1A1 gene. This gene encodes a protein that modifies hepatic bilirubin in order to allow it to be excreted. SNPs that reduce the activity of the UGT1A1 gene therefore tend to increase serum bilirubin levels.

The rs34815109(TA) allele represents the insertion variant, which actually adds a seventh (TA) pair to what is already a string of six (TA) pairs; this reduces the activity to 30% of normal, and is thus the risk allele. The risk allele is commonly referred to as the UGT1A1*28 allele, and it is homozygous in ~10% of the US population.[PMID 7565971]

Risks associated with the rs34815109(TA) allele are almost always associated with the homozygous (TA;TA) genotype, with smaller (or no) effects seen for rs34815109(-;TA) heterozygous carriers. These risks include:

  • An increased risk for breast cancer is reported in premenopausal African-American women, based on a study of 200 women. The reported odds ratio was 1.8 (CI: 1.0-3.1, p=0.06) for carriers of one or more UGT1A1*28 alleles.[PMID 10706110]
  • In colorectal cancer patients being treated with irinotecan, adverse side effects (neutropenia and/or severe diarrhea) are reported to be strongly associated with the number of UGT1A1*28 alleles. Patients homozygous for the *28 allele are 3.5 times more likely to develop severe neutropenia compared with individuals with the wild genotype.[PMID 19125129OA-icon.png] The FDA has approved a genetic test for UGT1A1 status to be used to determine dosage when considering irinotecan therapy [FDA press release]. However, no prospective study has examined whether a reduced dose of irinotecan results in a reduced rate of adverse drug events.[PMID 19125129OA-icon.png]

The three other SNPs that describe the same polymorphism are:

Neighborrs34983651
Distance1
Neighborrs5839491
Distance5