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瞬时受体电位(TRP)通道基因表达及TRP褪黑素(TRPM)通道基因多态性在肥胖相关代谢综合征中的作用

Role of the transient receptor potential (TRP) channel gene expressions and TRP melastatin (TRPM) channel gene polymorphisms in obesity-related metabolic syndrome.

作者信息

Tabur S, Oztuzcu S, Duzen I V, Eraydin A, Eroglu S, Ozkaya M, Demiryürek A T

机构信息

Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey.

出版信息

Eur Rev Med Pharmacol Sci. 2015 Apr;19(8):1388-97.

Abstract

OBJECTIVE

Metabolic syndrome (MetS) is correlated with increased cardiovascular risk and characterized by several factors, including visceral obesity, hypertension, dyslipidemia, and insulin resistance. The etiology of MetS is complex, and can be influenced by genetic susceptibility. The aim of this study was to investigate a possible association of transient receptor potential (TRP) channels gene expressions and TRP melastatin (TRPM) gene polymorphisms with MetS in a Turkish population.

PATIENTS AND METHODS

A total of 142 patients with obesity-related MetS and 166 healthy controls with similar age and sex were enrolled to this study. For polymorphism studies, genomic DNA from the participants was analyzed by a BioMark 96.96 dynamic array system (Fluidigm, South San Francisco, CA, USA). For gene expression studies, mRNA from blood samples was extracted, and real time polymerase chain reaction on the BioMark HD system was performed.

RESULTS

There was an increase in A allele (64.6% in patients vs. 49.5% in controls) and decrease in G allele frequencies (35.4% in patients vs. 50.5% in control, p = 0.0019) of the TRPM5 gene rs4929982 (Arg578Gln) polymorphism. We also observed that the distribution of genotype and allele frequencies of the TRPM8 gene rs12472151 in MetS patients were significantly different from controls (p < 0.0001). Although there were marked decreases in TRPC1, TRPC3, TRPM2, TRPM5, TRPV4, TRPV5, TRPV6, MCOLN2 (TRPML2), and MCOLN3 (TRPML3) gene expressions, an augmentation was noted in TRPC6 gene expression.

CONCLUSIONS

Genetic polymorphisms in TRPM5 and TRPM8 genes may modify individual susceptibility to MetS in the Turkish population. This study also revealed that there is a significant relationship between TRP channels gene expressions and MetS.

摘要

目的

代谢综合征(MetS)与心血管风险增加相关,其特征包括多种因素,如内脏肥胖、高血压、血脂异常和胰岛素抵抗。MetS的病因复杂,可能受遗传易感性影响。本研究旨在调查土耳其人群中瞬时受体电位(TRP)通道基因表达和TRP褪黑素受体(TRPM)基因多态性与MetS之间可能存在的关联。

患者与方法

本研究共纳入142例肥胖相关MetS患者和166例年龄、性别匹配的健康对照。对于基因多态性研究,采用BioMark 96.96动态阵列系统(美国加利福尼亚州南旧金山的Fluidigm公司)对参与者的基因组DNA进行分析。对于基因表达研究,提取血样中的mRNA,并在BioMark HD系统上进行实时聚合酶链反应。

结果

TRPM5基因rs4929982(Arg578Gln)多态性的A等位基因频率增加(患者中为64.6%,对照中为49.5%),G等位基因频率降低(患者中为35.4%,对照中为50.5%,p = 0.0019)。我们还观察到,MetS患者中TRPM8基因rs12472151的基因型和等位基因频率分布与对照相比有显著差异(p < 0.0001)。尽管TRPC1、TRPC3、TRPM2、TRPM5、TRPV4、TRPV5、TRPV6、MCOLN2(TRPML2)和MCOLN3(TRPML3)基因表达明显降低,但TRPC6基因表达有所增加。

结论

TRPM5和TRPM8基因的遗传多态性可能改变土耳其人群中个体对MetS的易感性。本研究还揭示了TRP通道基因表达与MetS之间存在显著关系。

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