Molecular basis of serological weak D phenotypes and RhD typing discrepancies identified in the Korean population.

BACKGROUND

The molecular basis of RhD blood groups differs with race/ethnicity. This study aimed to investigate the molecular basis of serological weak D phenotypes and RhD typing discrepancies in the Korean population.

MATERIALS AND METHODS

The RhD status of 188,852 Korean patients was initially determined using the automated microplate method and manual tile method. In case of no agglutination, weak D testing was further performed using the tube and gel methods. Serologically D-negative samples with C+ and/or E+ were tested using polymerase chain reaction-sequence specific primers for four RHD targets and/or exon 9 sequencing. Samples showing a serological weak D phenotype or an RhD typing discrepancy were subjected to full RHD gene sequencing.

RESULTS

Of the 32 samples showing a serological weak D phenotype and 191 samples showing a serologically D-negative phenotype with C+ and/or E+, 23 and 50 were genotyped, respectively. Among the weak D samples, the most common alleles were RHD15 (n=6), RHD13.01 (n=4), and RHD01W.25 (n=4), and no variant was found in two samples. RHD01EL.01 (n=26) accounted for more than half of the D-negative samples. Of the seven samples that were typed as D-positive using the automated microplate method but showed weak reactivity using the tile method, four were genotyped, and the results were as follows: RHD01W.33 (n=2), RHD01W.43 (n=1), and no variant found (n=1).

DISCUSSION

In our cohort, various D variant alleles including RHD15 were identified; however, RHD01W.1, RHD01W.2, RHD01W.3, RHD09.03.01, and RHD09.04, accounting for more than 95% of Caucasians with a serological weak D phenotype, were not found. Our study reaffirms that the distribution of D variant alleles differs between East Asians and Caucasians. Our findings also indicate that some D variants including RHD01W.33 and RHD01W.43 are at risk of being mistyped as D-positive by a highly sensitive RhD typing method such as an automated microplate method.