Allele and genotype frequencies of variants in P450 cytochromes, transports and DNA repair enzymes in the Dominican Republic population

Elizabeth Pérez-Duval ¹ Berniza Calderón ^1,2* Marlen Izquierdo ^1* José Alfredo Herrera Isidrón ³ Elizabeth Reyes Reyes ⁴ Alejandro Herrera ^5* Manuel Soto ² Alba Beltré ^1,2* Idania Rodeiro ^4*

• ¹ Santo Domingo Institute of Technology, Santo Domingo, Santo Domingo, Dominican Republic
• ² Centro Médico de Diabetes, Obesidad y Especialidades (CEMDOE), Santo Domigo, Dominican Republic
• ³ Institute of Materials Science and Technology, University of Havana, Havana, Cuba
• ⁴ Instituto de Ciencias del Mar (ICIMAR), La Habana, Cuba
• ⁵ Instituto de Ecología y Sistemática (CITMA), La Habana, Cuba

Single nucleotide variants give rise to important interindividual and interethnic variability in the metabolism and disposition of several therapeutic agents and may cause differences in the treatment response to clinical important drugs like antiarrhythmics, antidepressants, antihistamines antipsychotics, etc. Information about the prevalence of variants in the Dominican Republic population is still limited. The aim of the study was to describe the frequency distribution of 32 single nucleotide variants from fourteen genes with pharmacogenetic interest within a sample of 150 unrelated healthy individuals. Genotype and allele frequencies were determined and pairwise Wright’s Fst statistic was evaluated. Hardy-Weinberg equilibrium deviations were found in seven loci from CYP2D6 (rs16947, rs3892097, rs1058164, rs1135840, rs28371725) and CYP2C19 (rs12769205, rs4244285) genes. The Minor Allele Frequencies ranged from 0.01 to 0.50 values in the xenobiotic biotransformation enzymes and transporter genes. Average admixture estimates, respectively were: 51.6%, 39.5% and 8.9% for European, African and Amerindian ancestry. Pairwise Fst analysis revealed that Dominicans displayed genetic similarity to Latin American populations, especially the ones with Afro-Caribbean ancestry, given the selected variants. Higher differences were identified from East and South Asians, Europeans and Africans, in which several values above the Fst threshold for moderate differentiation were identified within variants in CYP2C, CYP3A, CYP1A1, ABCB1, SLC45A2, XRCC1 and XRCC3 genes. These results should allow establishing the clinical relevance of pharmacogenetic testing in variant alleles related to drug transport and metabolism genes in this population.