From SNPedia
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 19125129] 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 19125129]
The three other SNPs that describe the same polymorphism are:
