Molecular characterization of four alpha-1-antitrypsin variant alleles found in a Japanese population: a mutation hot spot at the codon for amino acid 362

Abstract

In this study alpha-1-antitrypsin (AAT) phenotypes at the protease inhibitor (PI) locus were determined by isoelectric focusing of native and desialylated serum samples from 236 Japanese subjects living in the western part of Japan. The shifts in relative mobility between some PI types were observed before and after desialylation. This technique was useful in distinguishing between some PI M subtypes and variants. The molecular basis of four variant alleles, including two new alleles found in this study, was characterized: PI E tokyo [Lys 335( AAG)→ Glu( GAG)] and PI N nagato [Leu 276(C TG)→Pro(C CG)] arose from PI M1(Val 213) and PI M2, respectively. A new PI P yonago [Asp 19(G AT)→Ala(G CT)] originated from PI M1(Val 213). A new PI M5 gunma [Pro 362( CCC)→Ser( TCC)], arising from PI M3, was the sixth allele involving a mutation at codon 362, which is suggested to be a mutation hot spot. PI M5 gunma was likely to show normal AAT levels and function although the mutations occurred near codon 358 for Met 358. The molecular basis of PI variant alleles found in Japanese was different from that reported in previous studies.