Molecular polymorphism of the Duffy system in an Argentinean population

COTORRUELO C; FIORI S; RACCA L; GARCÍA BORRÁS S; BIONDI C; RACCA A

Macao - Cina

Congreso; XXX Internationa Congress of the ISBT; 2008

International Society of Blood Transfusion

Background: the Duffy blood group locus is characterized by the three main alleles FY*A, FY*B, and FY*BES. The FY*A and FY*B alleles are distinguished by a missense mutation, which results in a single amino acid difference (G125A, Gly42Asp) and gives the common Fy(a+b-), Fy(a-b+) and Fy(a+b+) phenotypes in European and Asian populations. The Fy(a–b–) phenotype is commonly found in Blacks homozygous for the FY*BES which is caused by a substitution from T to C at the GATA box motif of the FY*B promoter (−33 T>C), disrupting the binding site for the GATA-1 erythroid transcription factor. Urban populations of Argentina are assumed to have a predominantly white Caucasian European genetic component. However, diverse ethnic-historic sources consider the Argentinean population to be a hybrid of Europeans, Amerindians and Africans. Aim of the study: to analyse the Duffy alleles and genotypes distribution in the population of Rosario, the third largest city of Argentina. Methods: blood samples from 206 self-identified white blood donors were studied. Duffy genotyping was performed by PCR strategies using primers designed with the allele-differentiating base at the 3’ position. Two PCR reactions each containing a forward primer (nucleotide -33T at the 3’ end) to target the normal FY alleles’ promoter region paired with reverse primers specific to anneal FY*A and FY*B (C125 and T125 at the 3’ end) alleles respectively were set up. The FY*BES allele was detected with a forward primer that anneal the mutated promoter region (-33C at the 3’ end) paired with the FY*B specific primer. The allele frequencies were determined by maximum likelihood methods and the genetic admixture was estimated through the ADMIX program. Results: the frequencies of the three major alleles differed significantly from those reported for Whites by molecular methods. An increased in the frequency of the FY*A (0.5073 vs. 0.3950) and FY*BES (0.0364 vs. 0.0100) alleles was found while the FY*B allele frequency was reduced (0.4563 vs. 0.5950) (p<0.005). Fifteen individuals of the sample carried the FY*BES allele and all of them were heterozygous. FY*A/FY*A (0.2913 vs. 0.1900), FY*A/FY*BES (0.0437 vs. 0.0200) and FY*B/FY*BES (0.0291 vs. 0.0000) genotypes frequencies were increased (p<0.001) while FY*B/FY*B (0.2476 vs. 0.4100) was reduced (p<0.001). No difference was found in the FY*A/FY*B (0.3883 vs. 0.3800) genotype frequency. The estimated African admixture based on the frequency of the FY*BES allele was 3.96%, with an associated standard error of 0.5%. Conclusions: the elevated frequencies found for the FY*A allele accounts for the Native American genetic contribution since Amerindians are characterized by a prevalence of these genetic markers. The detection of FY*BES reflect the contribution of African alleles to the genetic pool of the population under study and is useful to estimate its genetic admixture. The detection of FY*BES in Fyb(-) individuals will allow the administration of Fyb(+) units without risk of immunization since these patients express normal levels of FY*B product in tissues other than erythrocytes and thus they would not mount an immune response.