medRxiv : the preprint server for health sciences · 2026
The Alpha-1 Antitrypsin Z-allele associates with sarcopenia in the UK Biobank.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Attaway Amy, Serban Karina, Dutta Shovan, Hatipoğlu Umur, Zein Joe, Bazeley Peter, Kyriakidou Maria, Dawson Jennifer E, Ruvuna Lisa, Chad Wade R, Tejwani Vickram, Bon Jessica, Michael Wells J, Ortega Victor, Stoller James K, Bowler Russell
Аннотация
BACKGROUND: Sarcopenia is common in chronic obstructive pulmonary disease (COPD) and contributes to adverse outcomes. Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause of COPD, but its impact on skeletal muscle remains to be determined.
METHODS: We performed a retrospective analysis of 487,207 participants in the UK Biobank with available SERPINA1 genotyping. Associations between AAT genotypes and measures of skeletal muscle mass were determined using multivariable linear and logistic regression models. Models adjusted for age, sex, smoking status, genetic principal components, lung function (FEV₁% predicted), and liver fibrosis risk (FIB-4). We determined that the Z-allele was associated with sarcopenia and mortality using regression models and mediation analysis.
RESULTS: Compared with PI*MM individuals, carriers of the Z allele (PI*MZ, PI*SZ, PI*ZZ) demonstrated significantly lower fat free mass index (FFMI) and appendicular skeletal muscle index (ASMI), as well as higher odds of sarcopenia by binary definition. Associations persisted after adjustment for lung and liver function. A dose-dependent relationship was observed, with the greatest reductions in muscle mass and highest sarcopenia associated with PI*ZZ individuals (adjusted OR for FFMI-defined sarcopenia 2.02, 95% CI 1.16-3.32). Each additional Z allele was associated with increased mortality risk (adjusted OR 1.09, 95% CI 1.02-1.16), with sarcopenia mediating a modest proportion (∼2.6%) of this association.
CONCLUSIONS: The SERPINA1 Z allele is associated with reduced muscle mass and increased risk for sarcopenia independent of lung and liver disease. Our findings expand the phenotypic spectrum of AATD-related diseases to include skeletal muscle as a modifiable target for intervention.
METHODS: We performed a retrospective analysis of 487,207 participants in the UK Biobank with available SERPINA1 genotyping. Associations between AAT genotypes and measures of skeletal muscle mass were determined using multivariable linear and logistic regression models. Models adjusted for age, sex, smoking status, genetic principal components, lung function (FEV₁% predicted), and liver fibrosis risk (FIB-4). We determined that the Z-allele was associated with sarcopenia and mortality using regression models and mediation analysis.
RESULTS: Compared with PI*MM individuals, carriers of the Z allele (PI*MZ, PI*SZ, PI*ZZ) demonstrated significantly lower fat free mass index (FFMI) and appendicular skeletal muscle index (ASMI), as well as higher odds of sarcopenia by binary definition. Associations persisted after adjustment for lung and liver function. A dose-dependent relationship was observed, with the greatest reductions in muscle mass and highest sarcopenia associated with PI*ZZ individuals (adjusted OR for FFMI-defined sarcopenia 2.02, 95% CI 1.16-3.32). Each additional Z allele was associated with increased mortality risk (adjusted OR 1.09, 95% CI 1.02-1.16), with sarcopenia mediating a modest proportion (∼2.6%) of this association.
CONCLUSIONS: The SERPINA1 Z allele is associated with reduced muscle mass and increased risk for sarcopenia independent of lung and liver disease. Our findings expand the phenotypic spectrum of AATD-related diseases to include skeletal muscle as a modifiable target for intervention.