title: [Alpha 1-antitrypsin genes in patients with alpha 1AT deficiency in Japan: mutational analysis and allelic background].
abstract: Deficiency of alpha 1-antitrypsin (alpha 1AT), a plasma serine protease inhibitor, increases the risk of precocious pulmonary emphysema. Patients with alpha 1AT deficiency in Japan are extremely rare and no Z type alpha 1AT deficiency, which is one of the most frequent genetic disorders among Caucasians, are reported in Japan at the level of gene analysis. It is not yet clear why Z type alpha 1AT is rare among Japanese. When Ala213(GCG)-Val213(GTG) mutation in the alpha 1AT gene was examined by restriction endonuclease BstPI, all of 156 Japanese samples were Val213(GTG) in contrast to the finding that 30% of U.S. Caucasians are Ala213(GCG), indicating that alpha 1AT genes among Japanese were diverted from M1(Val213) variant and are different from M1(Ala213) variant, from which Z variant was likely diverted. This may explain why Z type alpha 1AT deficiency is not found among Japanese. A new alpha 1AT deficient variant, Siiyama (Ser53(TCC)-Phe53(TTC)), was found in a 39-year-old male with pulmonary emphysema (Seyama K, et al, J Biol Chem, 266, 12627, 1991). Interestingly, 6 out of 10 families with alpha 1AT deficiency in Japan shared the identical substitution as Siiyama. This indicates that although Caucasian type Z alpha 1AT deficiency is not found, Siiyama variant may be relatively common in Japan and even in other oriental countries because of the historical migration of people.
authors.affiliation: Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nukiwa
authors.forename: K
authors.initials: K
authors.lastname: Seyama
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Kira
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D005091:Exons; D014644:Genetic Variation; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D017354:Point Mutation; D011656:Pulmonary Emphysema / Q000209:etiology; D000515:alpha 1-Antitrypsin / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency
chemical_list: D000515:alpha 1-Antitrypsin