Sleep disruption and duration are associated with variants in genes involved in energy homeostasis in adults with HIV/AIDS

Abstract

Objective: To determine whether selected genes and plasma markers involved in energy homeostasis are associated with sleep disruption or duration in adults with HIV/AIDS. Methods: A sample of 289 adults with HIV/AIDS wore a wrist actigraph for 72 hours to estimate total sleep time (TST) and wake after sleep onset (WASO). Twenty-three single nucleotide polymorphisms (SNP) spanning 5 energy homeostasis genes (adiponectin [ADIPOQ], ghrelin [GHRL], leptin [LEP], peroxisome proliferator-activated receptor-alpha [PPARA], and -gamma [PPARG]) were genotyped using a custom array. Plasma markers of energy homeostasis (adiponectin, ghrelin, leptin) were measured by commercial multiplex assay.Results: After adjusting for demographic and clinical characteristics (race/ethnicity, gender, CD4 cell count, waist circumference, medications), both WASO and TST were associated with SNPs in ADIPOQ (rs182052), LEP (rs10244329, rs3828942), PPARA (rs135551, rs4253655), and PPARG (rs709151). Additional SNPs in ADIPOQ were associated with WASO (rs1501299, rs3821799, rs6773957) and TST (rs2241766). TST was also associated with SNPs in GHRL (rs26802), LEP (rs11760956), PPARA (rs135547, rs8138102, rs4253776), and PPARG (rs12490265, rs796313).Many covariate-adjusted associations involved a significant interaction with markers of HIV (viral load, years since diagnosis). Among plasma markers, higher adiponectin was associated with less WASO, higher ghrelin and glucose levels with shorter TST, and higher leptin with longer TST.Conclusions: Replication of SNPs in all five genes and three plasma markers of energy homeostasis were associated with objective sleep measures. HIV disease influenced many of the associations. Findings strengthen evidence for associations between energy homeostasis genetics and poor sleep, and provide direction for pharmacological intervention research.

Sleep Disturbance in the Context of HIV: A Concept Analysis

“…According to Alikhani et al (2020) , Chen et al (2021) , Daubert et al (2022) , Han et al (2021) , Ren et al (2018) , Wang et al (2021) , and Yan et al (2021) , psychological factors, such as depression, anxiety, and stress-related to living with a chronic illness, preceded sleep disturbance in PLWH. The second antecedent of sleep disturbance involves biological factors, including low CD4 cell levels ( Shi et al, 2020 ), high viral load ( Balthazar et al, 2021a ), genetic involvement ( Aouizerat et al, 2021 ; Ding et al, 2018 ), sex ( De Francesco et al, 2021a ; Moore et al, 2020 ), brain damage ( Happe, 2020 ; Leone et al, 2021 ), disease progress and duration ( Faraut et al, 2018b ; Milinkovic et al, 2020 ), and decreased immune function ( Babson et al, 2013 ; Low et al, 2012 ; Taibi et al, 2013 ).…”

“…Accordingly, identifying the concept's attributes is the primary goal of the concept analysis (Rodgers, 2000). In this analysis, two main attributes of sleep disturbance in the context of HIV were identified: a) subjective measures, including reduced total sleep (Aouizerat et al, 2021;dos Santos et al, 2018;Faraut et al, 2018aFaraut et al, , 2021Hixon et al, 2020;Santos et al, 2018), difficulty falling asleep, nighttime and early morning awakenings, feeling sleepy and poorly rested after a night's sleep, frequent arousal, and irritability (American Academy of Sleep Medicine, 2014a), and b) objective measures, including changes in sleep architecture and sleep continuity (Shikuma et al, 2018). During the analysis, it was found that only a few authors explicitly defined what they meant by sleep disturbance in the context of HIV.…”

“…The concept of sleep disturbance has been used inconsistently in the HIV context. Although sleep disturbanc e was most used among the terms referring to similar concepts, several other concepts have been used interchangeably, including poor sleep ( Abdu & Dule, 2020 ; Alikhani et al, 2020 ; Cody et al, 2020 ), sleep complaint ( Faraut et al, 2021 ; González-Tomé et al, 2018 ), sleep difficulty ( Mahmood et al, 2018 ), sleep disruption ( Aouizerat et al, 2021 ; Hixon et al, 2020 ), sleep pattern problem ( Bedaso et al, 2020 ), sleep alteration ( Moore et al, 2020 ), sleep disorder ( Chen et al, 2021 ; Chenxi et al, 2019 ), and insomnia ( Buchanan et al, 2018 ; Cody et al, 2020 ; Luu et al, 2022 ; Pujasari et al, 2020 ). Many previous researchers have undertaken studies to examine sleep among PLWH; however, there is no consensus on an accurate definition of sleep disturbance.…”

Gene Polymorphisms of Hormonal Regulators of Metabolism in Patients with Schizophrenia with Metabolic Syndrome

“…The polymorphism rs3828942 corresponds to a variation in the intron domain of the LEP gene. This polymorphism has nevertheless been repeatedly shown to be associated with clinical CNS-related phenomena [44][45][46][47]. Therefore, it may be shown that this polymorphism itself, or a polymorphism with rs3828942 in equilibrium, has functional consequences.…”