Genotypic and allelic variability in CYP19A1 among populations of African and European ancestry

Athena Davenport, Mohammed S. Orloff, Ishwori Dhakal, Rosalind B. Penney, Susan A. Kadlubar

Research output: Contribution to journalArticle

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Abstract

CYP19A1 facilitates the bioconversion of estrogens from androgens. CYP19A1 intron single nucleotide polymorphisms (SNPs) may alter mRNA splicing, resulting in altered CYP19A1 activity, and potentially influencing disease susceptibility. Genetic studies of CYP19A1 SNPs have been well documented in populations of European ancestry; however, studies in populations of African ancestry are limited. In the present study, ten 'candidate' intronic SNPs in CYP19A1 from 125 African Americans (AA) and 277 European Americans (EA) were genotyped and their frequencies compared. Allele frequencies were also compared with HapMap and ASW 1000 Genomes populations. We observed significant differences in the minor allele frequencies between AA and EA in six of the ten SNPs including rs10459592 (p<0.0001), rs12908960 (p<0.0001), rs1902584 (p = 0.016), rs2470144 (p<0.0001), rs1961177 (p<0.0001), and rs6493497 (p = 0.003). While there were no significant differences in allele frequencies between EA and CEU in the HapMap population, a 1.2- to 19-fold difference in allele frequency for rs10459592 (p = 0.004), rs12908960 (p = 0.0006), rs1902584 (p<0.0001), rs2470144 (p = 0.0006), rs1961177 (p<0.0001), and rs6493497 (p = 0.0092) was observed between AA and the Yoruba (YRI) population. Linkage disequilibrium (LD) blocks and haplotype clusters that is unique to the EA population but not AA was also observed. In summary, we demonstrate that differences in the allele frequencies of CYP19A1 intron SNPs are not consistent between populations of African and European ancestry. Thus, investigations into whether CYP19A1 intron SNPs contribute to variations in cancer incidence, outcomes and pharmacological response seen in populations of different ancestry may prove beneficial.

Original languageEnglish (US)
Article numbere0117347
JournalPLoS One
Volume10
Issue number2
DOIs
StatePublished - Feb 3 2015
Externally publishedYes

Fingerprint

Polymorphism
ancestry
Nucleotides
single nucleotide polymorphism
Single Nucleotide Polymorphism
Gene Frequency
gene frequency
African Americans
Introns
Population
HapMap Project
introns
Bioconversion
Androgens
Disease Susceptibility
Linkage Disequilibrium
Estrogens
linkage disequilibrium
Genes
androgens

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Genotypic and allelic variability in CYP19A1 among populations of African and European ancestry. / Davenport, Athena; Orloff, Mohammed S.; Dhakal, Ishwori; Penney, Rosalind B.; Kadlubar, Susan A.

In: PLoS One, Vol. 10, No. 2, e0117347, 03.02.2015.

Research output: Contribution to journalArticle

Davenport, Athena ; Orloff, Mohammed S. ; Dhakal, Ishwori ; Penney, Rosalind B. ; Kadlubar, Susan A. / Genotypic and allelic variability in CYP19A1 among populations of African and European ancestry. In: PLoS One. 2015 ; Vol. 10, No. 2.
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