title: E variants found in Japanese and c antigenicity alteration without substitution in the second extracellular loop.
abstract: BACKGROUND
  The molecular basis of E variants in the Japanese population is poorly understood. In this study, molecular analysis of E variants detected in Japanese by serologic methods was carried out.
  
  
  METHODS
  E variants from healthy Japanese blood donors were screened by serologic analysis using E MoAbs. Fifteen E variant samples were 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 from each other, those of the EFM-type variants (RHEFM) had a partial DNA exchange in exon 5 between the RHCE and RHD genes, generating an RHcE variant (Gln233Glu, Met238Val). The cDNA of EKH-type variants (RHEKH) exhibited a point mutation (G461C) in exon 3 of the RHcE allele that resulted in an Arg154Thr substitution in the third external loop of the RhcE peptide. The EKK-type variant (RHEKK) carried a hybrid gene structure characterized by replacement of exons 1-3 (or 2-3) of the RHCE gene with those of the RHD gene. The 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.
  
  
  CONCLUSIONS
  In serologic screening of 140,723 Japanese blood donors, 15 were found to possess E variants (0.011%). A new RHCE variant, RHEKH, was identified. On the basis of the variants found in this study, the c antigenicity 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.
authors.affiliation: Department of Research, Japanese Red Cross Central Blood Center, Shibuya-ku, Tokyo, Japan. kasiwase@cbc.jrc.or.jp
authors.forename: K
authors.initials: K
authors.lastname: Kashiwase
authors.forename: Y
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: H
authors.initials: H
authors.lastname: Hyodo
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Ogawa
authors.forename: H
authors.initials: H
authors.lastname: Tsuneyama
authors.forename: C
authors.initials: C
authors.lastname: Toyoda
authors.forename: M
authors.initials: M
authors.lastname: Uchikawa
authors.forename: T
authors.initials: T
authors.lastname: Akaza
authors.forename: M
authors.initials: M
authors.lastname: Omine
authors.forename: T
authors.initials: T
authors.lastname: Juji
mesh_terms: D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D001782:Blood Donors; D014644:Genetic Variation; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007519:Isoantigens / Q000235:genetics* / Q000276:immunology; D007564:Japan; D008403:Mass Screening; D017434:Protein Structure, Tertiary / Q000235:genetics; D012016:Reference Values; D012204:Rh-Hr Blood-Group System / Q000235:genetics*
chemical_list: D006023:Glycoproteins; D007519:Isoantigens; C066468:RHCE protein, human; D012204:Rh-Hr Blood-Group System