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.

Keywords: Epidermal growth factor, single nucleotide polymorphism, population genetics, ancestry, biomarker, pharmacogenomic marker.