Comprehensive analysis of RHD alleles in Argentineans with variant D phenotypes

Abstract

BACKGROUND: The serologic assignment of the D antigen status may be hindered in patients with weak D expression hampering clinical decision making in transfusion and obstetric medicine. A comprehensive study of RHD alleles occurring in the mixed population of Argentina is necessary to evaluate the most suitable DNA typing strategy. STUDY DESIGN AND METHODS: A total of 18378 patients from two stratified groups: G1 (public hospital) and G2 (private laboratory) were RhD phenotyped and 88 weakly reacting samples underwent molecular characterization. RESULTS: The frequency of D positive, D negative and variant D phenotypes differed significantly (p<0.001) between G1 and G2 (94.49% vs 87.66%, 5.15% vs 11.58%, 0.36% vs 0.75%, respectively). Eleven different alleles were responsible for the weak D expression. Approximately 60% of the weakly reacting samples from G1 and G2 were weak D types 1 through 4.0/4.2 and 25% were D category VII. RHD alleles associated with African ancestry were encountered in G1. A new G>A mutation at the D specific position -282 within the promoter region of DAU-4 and DOL alleles was identified. Three weak D type 1 samples with a ccee phenotype were found in G1. CONCLUSIONS: The D phenotype distribution found in G2 resembles that in Europeans while the frequencies in G1 may account for the Amerindian and African genetic contribution. The genotyping strategy used in this work is suitable to study the variant D phenotypes present in the overall population and could allow a better use of the few available D negative units as well as a more rationale administration of anti-D immunoglobulin. The results also show that weak D type 1 alleles do not exclusively segregate with a Ce allele, as assumed until present.