Prevalence of the DPYD variant (Y186C) in Brazilian individuals of African ancestry

Cancer Chemother Pharmacol. 2019 Dec;84(6):1359-1363. doi: 10.1007/s00280-019-03974-4. Epub 2019 Oct 22.

Abstract

Purpose: The presence of deleterious variants of dihydropyrimidine-dehydrogenase gene (DPYD) is associated with 5-Fluorouracil toxicity. Most of the data are based on findings in Caucasian populations. The variant Y186C (rs115232898) is found almost exclusively in African populations and is related to low DPD function. Its prevalence may vary among African subpopulations and in African Americans. There is no information in other populations. Brazil has the biggest African population outside Africa. We studied for the first time the frequency of this mutation in African Brazilians.

Methods: We amplified exon 6 of DPYD extracted from genomic DNA of 79 healthy volunteers of genetically defined African ancestry from Southeast Brazil and 36 self-reported African descendants from Northeast Brazil in order to determine the prevalence of the variant Y186C in Brazilians of African ancestry.

Results: The variant Y186C was found in heterozygosity in two samples from Southeast (2.53%) and one from Northeast (2.77%) Brazil. Overall, the prevalence of this mutation in the 115 African Brazilians was 2.6%.

Conclusions: The variant Y186C is prevalent among Brazilians of African ancestry and should be taken in account in targeted genotyping for fluoropyrimidine risk variants.

Keywords: 5-Fluorouracil; DPYD variant; Y186C.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Antimetabolites, Antineoplastic / therapeutic use
  • Black People / genetics*
  • Black or African American
  • Brazil / epidemiology
  • Capecitabine / pharmacokinetics
  • Capecitabine / therapeutic use
  • Dihydropyrimidine Dehydrogenase Deficiency / ethnology*
  • Dihydropyrimidine Dehydrogenase Deficiency / genetics
  • Dihydrouracil Dehydrogenase (NADP) / genetics*
  • Dihydrouracil Dehydrogenase (NADP) / metabolism
  • Female
  • Fluorouracil / pharmacokinetics
  • Fluorouracil / therapeutic use
  • Healthy Volunteers
  • Humans
  • Male
  • Mutation
  • Neoplasms / drug therapy
  • Prevalence

Substances

  • Antimetabolites, Antineoplastic
  • Capecitabine
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil