Genotyping of UGT1A1*80 as an Alternative to UGT1A1*28 Genotyping in Spain

Abstract

Background: The variant rs34983651 (UGT1A1*28) and its genotyping are used to prevent irinotecan-induced toxicity. Several variants are in close linkage disequilibrium. Our objective was to evaluate the potential correlation of genotyping UGT1A1*80 instead of UGT1A1*28 in different populations. Methods: We studied SNPs in linkage disequilibrium with UGT1A1*28 in several populations and selected rs887829 to develop an inexpensive and rapid genotyping method and compare it with the one we currently use for UGT1A1*28 genotyping. Samples from cancer patients (n = 701) already tested using PCR and electrophoresis prior to treatment with irinotecan for rs34983651 (UGT1A1*28) in a Spanish hospital were genotyped for rs887829 (UGT1A1*80) using real-time PCR with a TaqMan probe. Results: We observed a complete match for both genotypes, except in one sample. This method was 100% efficient in correctly genotyping *28/*28 patients, 99.68% efficient for *1/*28, and 100% efficient for *1/*1. Linkage disequilibrium between populations showed the Iberian population to be the most suitable for the clinical use of UGT1A1*80. This method is less expensive and the time to decision is shorter. Conclusion: Genotyping of rs887829 using the proposed method may be used to substitute genotyping of rs34983651 as a pharmacogenetics test in cancer patients prior to starting irinotecan-based treatments, mainly in the Iberian population. In addition, it is less expensive than other conventional methods and easy to implement, with a shorter time to decision than UGT1A1*28.

Statin Lactone Metabolism is a Determinant of 5-year Cardiovascular Outcomes Independent of Serum Cholesterol

“…Growing evidence indicates an important role for UGT1A enzymes in statin ADME 23 . UGT1A enzymes are responsible for glucuronidation and, through a subsequent elimination reaction, production of statin lactones 11 with specific SNP's recently characterized for their effect on metabolic function 24,25,26,27 and lactonization rates 28,29 . Supportive of our mechanistic hypothesis, UGT1A polymorphisms that increase UGT1A activity showed increased plasma lactone and also predicted adverse clinical outcomes (Supplemental Discussion).…”

Clinical and genetic definition of serum bilirubin levels for the diagnosis of Gilbert syndrome and hypobilirubinemia

“…We did not study the possible association of survival with other loci, such as the solute carrier organic anion transporter family member 1B1, which is also strongly associated with bilirubin levels. 46 …”

“…FIB4 was the fibrosis score computed with the data available in the UKB but has been shown to be a poor predictor of fibrosis in patients with NAFLD 46 and has worse performance in older patients, which has the potential to further skew the data over time. 15 …”