Allelic frequency of pathogenic α1-antitrypsin variants in the Japanese population: Results from a survey of open Japanese genetic variation databases

Abstract

α₁-antitrypsin deficiency (AATD) is a hereditary disorder with a global prevalence that differs across regions. AATD is highly prevalent in Europe and North America but rarely found in Asian countries, including Japan, possibly because of the founder effect of the pathogenic SERPINA1 variants PI*Z and PI*S. However, AATD remains underdiagnosed even in high-prevalence and low-prevalence regions, possibly because of lack of awareness. In this study, we surveyed open Japanese genetic variation databases to estimate AATD prevalence in Japan. We identified allelic frequencies (AFs) of 5 among the 14 major pathogenic SERPINA1 variants from three datasets, collectively derived from 63,119 Japanese participants. The mean AF was determined to be 8.56 × 10⁻⁴ (95% confidence interval [CI]: 6.43 × 10⁻⁴ to 1.12 × 10⁻³). Given that this represents the entire Japanese population, one AATD patient was speculated to be born per 1.37 × 10⁶ births (95% CI: 7.97 × 10⁵ to 2.42 × 10⁶) in Japan. Our results support the prevailing notion that AATD is extremely rare in Japan.