Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1138-1143
PLENARY PAPER
Simple PCR detection of haptoglobin gene deletion in
anhaptoglobinemic patients with antihaptoglobin antibody that causes
anaphylactic transfusion reactions
Yoshiro Koda,
Yoshihisa Watanabe,
Mikiko Soejima,
Eiko Shimada,
Motoko Nishimura,
Kaichiro Morishita,
Susumu Moriya,
Shigeki Mitsunaga,
Kenji Tadokoro, and
Hiroshi Kimura
From the Division of Human Genetics, Department of Forensic
Medicine, Kurume University School of Medicine, Kurume; Transfusion
Information Department, The Japanese Red Cross Central Blood Center,
Tokyo; Department of Gynaecology, Masuda Red Cross Hospital, Masuda;
and Department of Medicine, Tokyo Metropolitan Hiroo Hospital, Tokyo,
Japan.
Two anhaptoglobinemic patients showing anaphylactic transfusion
reactions by antihaptoglobin antibody were found. Southern blot
analysis indicated that 2 patients were homozygous for the deleted
allele of the haptoglobin gene (Hpdel)
as reported previously. We have identified the junction region of the
deletion from genomic DNA of 1 patient using cassette-mediated polymerase chain reaction (PCR). Then, the deleted region
from the 5' breakpoint to the promoter region of the Hp
was amplified from genomic DNA of a control individual using PCR. DNA
sequence analysis of these regions indicated that the 5'
breakpoint of the Hpdel allele was located
5.2 kilobase (kb) upstream of exon 1 of the Hp and the 3'
breakpoint was positioned between 52 and 53 base pair (bp) upstream of
exon 5 of the haptoglobin-related gene. There was no significant
homology between the DNA sequences flanking the 5' and 3'
breakpoints, except for a 2-bp (TG) identity. To examine the gene
frequency, we have developed a simple PCR method to detect the gene
deletion. We found 8, 16, and 17 Hpdel
alleles in 157 Koreans, 523 Japanese, and in 284 Chinese, respectively, but did not find the Hpdel in 101 Africans
or in 100 European-Africans. The incidence of individuals
homozygous for the Hpdel allele was
therefore expected to be 1/4000 in Japanese, 1/1500 in Koreans, and
1/1000 in Chinese. This incidence is higher than that of IgA deficiency
in Japanese. More attention should be paid on haptoglobin deficiency
and antihaptoglobin antibody as the cause of transfusion-related
anaphylactic reactions in Asian populations.
