Center for Sleep and Circadian Neurobiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Emory University, Nell Hodgson Woodruff School of Nursing, Atlanta, GA, USA.
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
Sleep Med. 2018 Jul;47:106-112. doi: 10.1016/j.sleep.2017.12.010. Epub 2018 Jan 12.
Sleepiness and cardiovascular disease share common molecular pathways; thus, genetic risk factors for sleepiness may also predict cardiovascular disease risk. This study explored the associations between subjective sleepiness and single-nucleotide polymorphisms (SNPs) in candidate genes within oxidative stress, inflammatory, and neuronal pathways, which may contribute to sleepiness and downstream cardiovascular disease risk: Cytochrome B-245, Alpha Polypeptide (CYBA), Cytochrome B-245, Beta Polypeptide (CYBB), Neutrophil Cytosolic Factor (NCF2), Tumor Necrosis Factor-Alpha (TNFA), and Phosphodiesterase 4D (PDE4D).
Adults (N = 918) from the general population who were a part of the São Paulo Epidemiologic Sleep Study (EPISONO) in São Paulo, Brazil, were genotyped using Human Omni Express BeadChip array. The average age was 42 ± 14.5 years, subjects had a mean body mass index (BMI) of 26.9 ± 5.4 kg/m, and 44% were male. Based on the Epworth Sleepiness Scale (ESS), subjects were classified as having sleepiness (ESS ≥ 10) or no sleepiness (ESS < 10). Logistic regression models were used to examine the associations with SNPs within candidate genes and sleepiness, adjusting for age, gender, BMI, Apnea-Hypopnea Index (AHI), total sleep time, and ancestry informative principal components (PCs). Complementary analyses using linear regression to assess the relationship between SNPs and continuous ESS were performed.
We observed a novel association between the C allele of the rs12522161 SNP on PDE4D and a decreased likelihood of sleepiness, controlling for covariates and ancestry [OR (95% CI) = 0.64 (0.50, 0.81); p = 0.0002].
We present data for a novel genetic association with sleepiness for an SNP on the PDE4D gene, rs12522161.
困倦和心血管疾病有共同的分子途径；因此，困倦的遗传风险因素也可能预测心血管疾病的风险。本研究探讨了主观困倦与氧化应激、炎症和神经元途径中候选基因的单核苷酸多态性（SNP）之间的关联，这些基因可能导致困倦和下游心血管疾病的风险：细胞色素 B-245，α 多肽（CYBA）、细胞色素 B-245，β 多肽（CYBB）、中性粒细胞胞质因子（NCF2）、肿瘤坏死因子-α（TNFA）和磷酸二酯酶 4D（PDE4D）。
来自巴西圣保罗的一般人群中参与圣保罗流行病学睡眠研究（EPISONO）的成年人（N=918）使用人类全基因组表达珠芯片阵列进行基因分型。平均年龄为 42±14.5 岁，受试者平均体重指数（BMI）为 26.9±5.4kg/m，44%为男性。根据埃普沃思嗜睡量表（ESS），将受试者分为嗜睡（ESS≥10）或无嗜睡（ESS<10）。使用逻辑回归模型，在调整年龄、性别、BMI、呼吸暂停低通气指数（AHI）、总睡眠时间和祖先信息主成分（PCs）后，研究候选基因内的 SNPs 与困倦之间的关联。使用线性回归进行补充分析，以评估 SNPs 与连续 ESS 之间的关系。
我们观察到 PDE4D 基因上 rs12522161 位点的 C 等位基因与困倦的可能性降低之间存在新的关联，在控制了协变量和祖先后[比值比（95%置信区间）=0.64（0.50, 0.81）；p=0.0002]。
我们提出了一个关于 PDE4D 基因上 rs12522161 位点与困倦的新的遗传关联数据。
