Polymorphisms in the coding region of mtDNA and effects on clinical outcome of unrelated bone marrow transplantation.
The entire protein-coding region was divided into 45 fragments, separately amplified and analyzed for polymorphism by the PCR-SSCP (single-strand conformation polymorphism) method. The effect of polymorphism mismatching on the clinical outcome of unrelated bone marrow transplantation was studied to clarify whether products from mtDNA become minor antigens. Variability in PCR-SSCP pattern combinations of the 45 fragments suggests that each individual has a different polymorphism combination in the protein-coding region if all the coding regions were compared at the nucleotide sequence level. Nonsynonymous polymorphisms were found at relatively high frequency in MTATP8 and MTND3. Both the polymorphisms with and without substitution matched the peptide-binding motifs of HLA-A*0201. The effects of the polymorphism matching were retrospectively analyzed in 340 recipients transplanted with HLA-A, -B, -DRB1 allele-matched bone marrow from unrelated donors. There were no effects of polymorphism matching on the incidence of acute GVHD and cumulative disease-free survival. These results suggest that polymorphisms which generate peptides, with and without substitutions, that bind the same HLA molecule hardly influence GVHD because the difference between the HLA-peptide complexes is minute.
Ishikawa
Y
Y
Japanese Red Cross Central Blood Center, Tokyo, Japan.
Kashiwase
K
K
Okai
M
M
Ogawa
A
A
Akaza
T
T
Morishima
Y
Y
Inoko
H
H
Sasazuki
T
T
Kodera
Y
Y
Juji
T
T
D016026:Bone Marrow Transplantation / Q000276:immunology*; D003573:Cytochrome b Group / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D018572:Disease-Free Survival; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D006086:Graft vs Host Disease / Q000235:genetics; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000235:genetics; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics; D009245:NADH Dehydrogenase / Q000235:genetics; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D014181:Transplantation Immunology / Q000235:genetics*; D014184:Transplantation, Homologous / Q000276:immunology; D016896:Treatment Outcome
D003573:Cytochrome b Group; D004272:DNA, Mitochondrial; D015778:Minor Histocompatibility Antigens; D009245:NADH Dehydrogenase; D025261:Mitochondrial Proton-Translocating ATPases