Bluestone Center for Clinical Research, New York University, NY, USA; Department of Oral and Maxillofacial Surgery, New York University, NY, USA.
Department of Biobehavioral Nursing and Health Informatics, University of Washington, Seattle, WA, USA.
Sleep Med. 2021 Jun;82:84-95. doi: 10.1016/j.sleep.2020.08.028. Epub 2020 Aug 28.
To determine whether selected genes and plasma markers involved in energy homeostasis are associated with sleep disruption or duration in adults with HIV/AIDS.
A sample of 289 adults with HIV/AIDS wore a wrist actigraph for 72 h 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.
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.
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.
确定与能量平衡相关的特定基因和血浆标志物是否与 HIV/AIDS 成人的睡眠中断或持续时间有关。
对 289 名 HIV/AIDS 成人进行了为期 72 小时的腕部活动记录仪佩戴,以估计总睡眠时间(TST)和睡眠后觉醒时间(WASO)。使用定制的数组对跨越 5 个能量平衡基因(脂联素[ADIPOQ]、胃饥饿素[GHRL]、瘦素[LEP]、过氧化物酶体增殖物激活受体-α[PPARA]和-γ[PPARG])的 23 个单核苷酸多态性(SNP)进行了基因分型。通过商业多重分析测量了能量平衡的血浆标志物(脂联素、胃饥饿素、瘦素)。
在调整了人口统计学和临床特征(种族/民族、性别、CD4 细胞计数、腰围、药物)后,WASO 和 TST 均与 ADIPOQ(rs182052)、LEP(rs10244329、rs3828942)、PPARA(rs135551、rs4253655)和 PPARG(rs709151)中的 SNP 相关。ADIPOQ 中的其他 SNP 与 WASO(rs1501299、rs3821799、rs6773957)和 TST(rs2241766)相关。TST 还与 GHRL(rs26802)、LEP(rs11760956)、PPARA(rs135547、rs8138102、rs4253776)和 PPARG(rs12490265、rs796313)中的 SNP 相关。许多经协变量调整的关联涉及与 HIV 标志物(病毒载量、诊断后年限)的显著相互作用。在血浆标志物中,较高的脂联素与较少的 WASO 相关,较高的胃饥饿素和葡萄糖水平与较短的 TST 相关,较高的瘦素与较长的 TST 相关。
对所有五个基因和三个能量平衡的血浆标志物的 SNP 进行复制,与客观的睡眠测量结果相关。HIV 疾病影响了许多关联。这些发现为能量平衡遗传学与睡眠质量差之间的关联提供了更多证据,并为药物干预研究提供了方向。