Title:Ancestry-Related Differences in Allele and Genotype Frequencies of EGF A61G Polymorphism in the Cuban Population
Volume: 21
Issue: 3
Author(s): Yaima Zuñiga-Rosales*, Goitybell Martínez-Téllez, Hilda Roblejo-Balbuena, Giselle Monzón-Benítez, Jonas Bybjerg-Grauholm, Ole Mors and Beatriz Marcheco- Teruel*
Affiliation:
- National Centre of Medical Genetics, Havana, Cuba
- University of Medical Science, Havana, Cuba
- National Centre of Medical Genetics, Havana, Cuba
- University of Medical Science, Havana, Cuba
Keywords:
Epidermal growth factor, single nucleotide polymorphism, population genetics, ancestry, biomarker, pharmacogenomic marker.
Abstract:
Background: The polymorphism rs4444903 of the Epidermal Growth Factor
gene (EGF A61G) causes differences in the EGF serum levels. It has become a biomarker
for genetic susceptibility to cancer and a pharmacogenomic marker for therapies involving
the EGF/EGF-receptor pathway.
Objective: The present study aimed to characterize the allele and genotype frequencies of
the rs4444903 in a Cuban sample and its relationship to a specific genetic ancestry.
Methods: A cross-sectional study was carried out. Genomic data was collected from a
dense genome-wide genotyping array analysis of 948 Cubans from all provinces. The allele
and genotype frequencies of the rs4444903 were calculated. Analysis of ancestryrelated
allelic/genotypic differences was performed.
Results: The frequencies for both alleles were found to be very similar (0.52 for G vs. 0.48
for A allele), and genotype frequencies were 24.3%, 47.9%, and 27.8% for AA, AG, and
GG, respectively. Greater differences were found between Cuban provinces, with frequencies
for the G allele ranging from 0.38 in Artemisa to 0.69 in Guantánamo and for the GG
genotype from 14.29% in Mayabeque to 50.88% in Guantánamo. An increased Africanancestry
proportion was related to a higher probability of carrying G allele and GG genotype,
with a significant (p=0.0038, q=0.024) African-ancestry-enrichment pattern
Conclusion: African ancestry seems to contribute to an increase in the EGF61*G allele in
Cubans. Geographic patterns in admixture proportions for African and European ancestry
are a determinant factor in the allelic and genotypic frequency differences between Cuban
provinces. Such differences should be observed when designing association studies and
implementing therapeutic approaches based on the EGF/EGF receptor pathway in Cuba.
