BACKGROUND: The molecular basis of E variants in the Japanese population is
poorly understood. In this study, molecular analysis of E variants detecte
d in Japanese by serologic methods was carried out.
STUDY DESIGN AND METHODS: E variants from healthy Japanese blood donors wer
e screened by serologic analysis using E MoAbs. Fifteen E variant samples w
ere divided into three types-EFM, EKH, and EKK-on the basis of patterns of
reactivity with five distinct E antibodies. The entire coding region of the
Rh cDNAs from the E variant samples was analyzed by sequencing.
RESULTS: Although the Rh cDNA sequences of the three types were different f
rom each other, those of the EFM-type variants (RHEFM) had a partial DNA ex
change in exon 5 between the RHCE and RHD genes, generating an RHcEvariant
(Gln233Glu, Met238Val). The cDNA of EKH-type variants (RHEKH) exhibited a p
oint mutation (G461C) in exon 3 of the RHcE allele that resulted in an Arg1
54Thr substitution in the third external loop of the RhcE peptide. The EKK-
type variant (RHEKK) carried a hybrid gene structure characterized by repla
cement of exons 1-3 (or 2-3) of the RHCE gene with those of the RHD gene, T
he RHD gene of a person possessing an E variant of the EKK type was also a
hybrid gene, D-cE(2-3)-D or cE(1-3)-D (RHDKK). The E variants of types EKH
and EKK showed weak c antigenicity.
CONCLUSION: In serologic screening of 140,723 Japanese blood donors, 15 wer
e found to possess E variants (0.011%). A new RHCE variant, RHEKH, was iden
tified. On the basis of the variants found in this study, the c antigenicit
y seemed to be determined not only by Pro-103 but also by the structure of
the third extracellular loop or the amino acids contained in it.