title: No association between dysplasminogenemia with p.Ala620Thr mutation and atypical hemolytic uremic syndrome.
abstract: Atypical hemolytic uremic syndrome (aHUS), a form of thrombotic microangiopathy, is caused by the uncontrolled activation of the alternative pathway of complement on the cell surface that leads to microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. A recent genetic analysis of aHUS patients identified deleterious mutations not only in complement or complement regulatory genes but also in the plasminogen gene, suggesting that subnormal plasminogen activity may be related to the degradation of thrombi in aHUS. Dysplasminogenemia, which is caused by a genetic variant in the plasminogen gene, PLG:p.Ala620Thr, is commonly observed in the northeast Asian populations, including Japanese. To examine the association between dysplasminogenemia and aHUS, we genotyped PLG:p.Ala620Thr in 103 Japanese patients with aHUS. We identified five aHUS patients with PLG:p.Ala620Thr; the minor allele frequency (MAF) was thus 0.024. The MAF in the patient group was not significantly different from those obtained from a general Japanese population (MAF = 0.020) and the Japanese genetic variation HGDV database (MAF = 0.021) (P = 0.62 and 0.61, respectively). We concluded that, although carriers with PLG:p.Ala620Thr show low plasminogen activity, this is not a predisposing variant for aHUS and that individuals of dysplasminogenemia are not at significantly increased risk of aHUS.
authors.affiliation: Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan. miyata@ncvc.go.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.affiliation: Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Uchida
authors.affiliation: Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.affiliation: Japanese Red Cross Kinki Blood Center, Ibaraki, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.affiliation: Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
mesh_terms: D044466:Asian People / Q000235:genetics; D065766:Atypical Hemolytic Uremic Syndrome / Q000235:genetics*; D003231:Conjunctivitis / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D010958:Plasminogen / Q000172:deficiency* / Q000235:genetics; D012873:Skin Diseases, Genetic / Q000235:genetics*
chemical_list: D010958:Plasminogen
keywords: Atypical hemolytic uremic syndrome; Fibrinolysis; Plasminogen abnormality; Race-specific variant; Thrombotic microangiopathy