iScience · 2025
Adaptive PRKAA1 variant in Andeans is associated with improved ventilation and sleep phenotypes.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Lawrence Elijah S, Gu Wanjun, Kong Mitchell C, Fassardi Santiago, Anza-Ramirez Cecilia, Moya Esteban A, Heinrich Erica C, Yu James J, Orr Jeremy E, Cao Steven Y, Sanchez-Azofra Ana, Cole Amy M, Hall James E, Lin Andrew, DeYoung Pamala N, Vizcardo-Galindo Gustavo, Macarlupu Jose-Luis, Figueroa-Mujíca Rómulo, Bermudez Daniela, Corante Noemi, Cavalleri Gianpiero L, Gaio Eduardo, Evans A Mark, Powell Frank L, Malhotra Atul, Salem Rany M, Villafuerte Francisco C, Simonson Tatum S
Аннотация
Highland groups have adapted to the extreme selective pressures of hypoxia at high altitude via alterations in the oxygen-transport cascade. PRKAA1, which encodes the catalytic subunit of the AMP-activated protein kinase (AMPK), is a notable target of natural selection in Andeans and has been associated with protective fetal phenotypes in this population. AMPK is a universal cellular energy sensor involved in a multitude of physiological processes, including ventilation and the hypoxic ventilatory response (HVR) in animal models. We localized a signal of positive selection and identified a regulatory promoter variant (rs10035235, C>T) of adaptive significance that is associated with ventilatory and sleep phenotypes in male Andean highlanders as well as sleep phenotypes in publicly available lowland cohorts. This work identifies a functional, adaptive, and likely pleiotropic regulatory variant in PRKAA1 in Andeans that may accentuate hypoxia-induced ventilation and provide protection from sleep-disordered breathing in both high- and lowland populations.