Candidate gene analysis in the São Paulo Epidemiologic Sleep Study (EPISONO) shows an association of variant in PDE4D and sleepiness.
Candidate gene analysis in the São Paulo Epidemiologic Sleep Study (EPISONO) shows an association of variant in PDE4D and sleepiness.
复制标题
圣保罗流行病学睡眠研究 (EPISONO) 的候选基因分析显示 PDE4D 变异与嗜睡之间存在关联。
DOI：
10.1016/j.sleep.2017.12.010
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发表时间：
2018
期刊：
影响因子：
4.8
通讯作者：
Tufik,Sergio
中科院分区：
文献类型：
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作者：
Pak,VictoriaM;Mazzotti,DiegoR;Keenan,BrendanT;Hirotsu,Camila;Gehrman,Philip;Bittencourt,Lia;Pack,AllanI;Tufik,Sergio
嗜睡与心血管疾病有共同的分子通路；因此，嗜睡的遗传风险因素也可以预测心血管疾病的风险。本研究探讨了可能导致嗜睡和下游心血管疾病风险的氧化应激、炎症和神经通路中候选基因的单核苷酸多态性（snp）与主观嗜睡之间的关系：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）。方法来自巴西<s:1>圣保罗流行病学睡眠研究（EPISONO）的普通人群（N = 918）的成年人使用Human Omni Express BeadChip阵列进行基因分型。平均年龄42±14.5岁，平均体重指数（BMI） 26.9±5.4 kg/m2，男性占44%。根据Epworth嗜睡量表（ESS），将受试者分为有嗜睡（ESS≥10）和无嗜睡（ESS < 10）。通过调整年龄、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）等因素，采用Logistic回归模型检验候选基因内snp与嗜睡之间的关系。使用线性回归进行补充分析，以评估snp与连续ESS之间的关系。结果我们观察到PDE4D上rs12522161 SNP的C等位基因与嗜睡可能性降低之间存在新的关联，控制了协变量和祖先[OR (95% CI) = 0.64 (0.50, 0.81)；p = 0.0002]。我们提供了PDE4D基因rs12522161上的一个SNP与嗜睡的新遗传关联的数据。
IntroductionSleepiness 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),andPhosphodiesterase 4D (PDE4D).MethodsAdults (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/m2, 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.ResultsWe 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].ConclusionWe present data for a novel genetic association with sleepiness for an SNP on the PDE4D gene, rs12522161.