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对 55 位阻塞性睡眠呼吸暂停患者进行载脂蛋白基因 L55M 多态性与对氧磷酶 1 活性的研究。

Paraoxonase 1 Gene L55M Polymorphism and Paraoxonase 1 Activity in Obstructive Sleep Apnea Patients.

机构信息

Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Poznań, Poland.

Department of Laboratory Diagnostics, Poznan University of Medical Sciences, Poznań, Poland.

出版信息

Adv Exp Med Biol. 2019;1150:17-24. doi: 10.1007/5584_2018_267.

Abstract

The antioxidant enzyme paraoxonase-1 (PON1) may limit oxidative stress in the development of cardiovascular diseases (CVD) and obstructive sleep apnea (OSA). The aim of the study was to determine PON1 gene L55M polymorphism in OSA-positive and OSA-negative subjects, along with paraoxonase activity of the enzyme (PON1-act). Caucasians aged 25-75, with BMI 19.0-53.0 kg/m and no acute or severe chronic disorder underwent polysomnography, and OSA-negative (n = 44) and OSA-positive (n = 57) groups were established. The following parameters were assessed: arterial blood pressure and serum glucose, lipids, C-reactive protein, and homocysteine. Genomic DNA was extracted and amplified, and automatic sequencing was used to confirm the LL, LM, MM genotypes. PON1-act was measured spectrophotometrically using paraoxon as a substrate. We found that frequency of polymorphisms differed significantly between the OSA-negative and OSA-positive patients (p < 0.05). Increased PON1-act was observed in the LL-genotype versus the LM + MM-genotype in the study population (p < 0.05). PON1-act was higher in the OSA-negative compared with OSA-positive patients (p < 0.001); in general and in the subgroups presenting the LL or LM genotype. In addition, there was an inverse relationship between PON1-act and LDL-cholesterol in the entire study population. The OSA-positive group presented an inverse relationship between PON1-act and fasting glucose. We conclude that patients could benefit from the LL genotype related with higher activity of PON1. OSA pathology might decrease the enzyme activity, despite the presence of L allele.

摘要

抗氧化酶对氧磷酶-1(PON1)可能限制心血管疾病(CVD)和阻塞性睡眠呼吸暂停(OSA)的氧化应激。本研究旨在确定 OSA 阳性和 OSA 阴性受试者中 PON1 基因 L55M 多态性,以及酶的对氧磷酶活性(PON1-act)。年龄在 25-75 岁、BMI 为 19.0-53.0kg/m2且无急性或严重慢性疾病的白种人接受多导睡眠图检查,并建立 OSA 阴性(n=44)和 OSA 阳性(n=57)组。评估以下参数:动脉血压和血清葡萄糖、脂质、C 反应蛋白和同型半胱氨酸。提取和扩增基因组 DNA,并使用自动测序确认 LL、LM、MM 基因型。使用对氧磷作为底物通过分光光度法测量 PON1-act。我们发现,PON1 基因多态性在 OSA 阴性和 OSA 阳性患者之间存在显著差异(p<0.05)。在研究人群中,与 LM+MM 基因型相比,LL 基因型的 PON1-act 增加(p<0.05)。与 OSA 阳性患者相比,OSA 阴性患者的 PON1-act 更高(p<0.001);在总体以及具有 LL 或 LM 基因型的亚组中也是如此。此外,在整个研究人群中,PON1-act 与 LDL-胆固醇呈负相关。OSA 阳性组的 PON1-act 与空腹血糖呈负相关。我们的结论是,PON1 活性较高的 LL 基因型的患者可能会受益。尽管存在 L 等位基因,但 OSA 病理可能会降低酶的活性。

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