CYP2D6 is a highly polymorphic gene whose variations affect its enzyme activity. To assess whether the specific population history of Roma, characterized by constant migrations and endogamy, influenced the distribution of alleles and thus phenotypes, the CYP2D6 gene was sequenced using NGS (Next Generation Sequencing) method-targeted sequencing in three groups of Croatian Roma (N = 323) and results were compared to European and Asian populations. Identified single nucleotide polymorphisms (SNPs) were used to reconstruct haplotypes, which were translated into the star-allele nomenclature and later into phenotypes. A total of 43 polymorphic SNPs were identified. The three Roma groups differed significantly in the frequency of alleles of polymorphisms 6769 A > G, 6089 G > A, and 5264 A > G (p < 0.01), as well as in the prevalence of the five most represented star alleles: *1, *2, *4, *10, and *41 (p < 0.0001). Croatian Roma differ from the European and Asian populations in the accumulation of globally rare SNPs (6089 G > A, 4589 C > T, 4622 G > C, 7490 T > C). Our results also show that demographic history influences SNP variations in the Roma population. The three socio-culturally different Roma groups studied differ significantly in the distribution of star alleles, which confirms the importance of a separate study of different Roma groups.
Keywords: ADME; CYP2D6; Croatia; Roma; pharmacogenetics; population genetics; star allele.