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人类瘦素基因 3'UTR 多态性及其在高血压中的作用。

Polymorphisms in the 3'UTR of the human leptin gene and their role in hypertension.

机构信息

Department of Biochemistry, University of Kashmir, Hazratbal, Jamuu and Kashmir 190 006, India.

出版信息

Mol Med Rep. 2012 Apr;5(4):1058-62. doi: 10.3892/mmr.2012.743. Epub 2012 Jan 4.

DOI:10.3892/mmr.2012.743
PMID:22218754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3493089/
Abstract

Leptin is a protein hormone, mainly synthesized in adipocytes, that regulates the food intake and energy expenditure of the body. Rare mutations in the leptin gene cause obesity. Common polymorphisms of the leptin gene have been associated with obesity, however their association with arterial blood pressure has not been fully elucidated. The aim of the present study was to examine the effect of variants in the 3' flanking region of the leptin gene on blood pressure in hypertensive subjects with high (35.2 ± 5.12) and low (20.13 ± 1.3) body mass index (BMI). Microsatellite polymorphisms and the C538T SNP in the 3'UTR of the leptin gene were screened in 362 subjects, and different biochemical and anthropometric parameters were measured. The levels of serum urea, creatinine, glucose, cholesterol, triglyceride, leptin and angiotensin II were determined in all subjects. A strong association of microsatellite polymorphisms with essential hypertension was found in subjects with a high BMI, but this association was only slight in subjects with a normal BMI. The C538T variant was not found in this population. The frequency of the Class I/Class I and Class I/Class II genotype for tetranucleotide polymorphisms was also significantly higher in the hypertensive compared to the normotensive group (p ≤ 0.0001). In addition, a significant correlation was found between serum leptin and Class I/I and Class I/II genotypes. Linear regression analysis showed an independent correlation of leptinemia with BMI (p=0.019), while a notable correlation was found between serum leptin concentration and angiotensin II. The study confirmed that shorter alleles of microsatellites in the 3' flanking region of leptin are significantly associated with hypertension, however, the underlying mechanism remains unknown.

摘要

瘦素是一种主要在脂肪细胞中合成的蛋白激素,调节机体的摄食和能量支出。瘦素基因的罕见突变可导致肥胖。瘦素基因的常见多态性与肥胖有关,但它们与动脉血压的关系尚未完全阐明。本研究旨在探讨瘦素基因 3'侧翼区变异对高(35.2±5.12)和低(20.13±1.3)体重指数(BMI)的高血压患者血压的影响。在 362 名受试者中筛选了瘦素基因 3'UTR 的微卫星多态性和 C538T SNP,并测量了不同的生化和人体测量参数。所有受试者均测定血清尿素、肌酐、葡萄糖、胆固醇、甘油三酯、瘦素和血管紧张素 II 水平。在高 BMI 的受试者中,微卫星多态性与原发性高血压有很强的相关性,但在正常 BMI 的受试者中这种相关性很弱。在该人群中未发现 C538T 变体。四核苷酸多态性的 I 类/ I 类和 I 类/ II 类基因型的频率在高血压组也明显高于正常血压组(p≤0.0001)。此外,血清瘦素与 I 类/ I 类和 I 类/ II 类基因型之间存在显著相关性。线性回归分析显示,瘦素血症与 BMI 呈独立相关(p=0.019),而血清瘦素浓度与血管紧张素 II 之间存在显著相关性。该研究证实,瘦素基因 3'侧翼区较短的微卫星等位基因与高血压显著相关,但具体机制尚不清楚。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95a2/3493089/3bd39850243a/MMR-05-04-1058-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95a2/3493089/ee677f0e80c3/MMR-05-04-1058-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95a2/3493089/3bd39850243a/MMR-05-04-1058-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95a2/3493089/ee677f0e80c3/MMR-05-04-1058-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95a2/3493089/3bd39850243a/MMR-05-04-1058-g02.jpg

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本文引用的文献

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Mol Cell Biochem. 2007 Aug;302(1-2):125-31. doi: 10.1007/s11010-007-9434-5. Epub 2007 Mar 1.
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Lack of association between the tetranucleotide repeat polymorphism in the 3'-flanking region of the leptin gene and hypertension in severely obese patients.瘦素基因3'侧翼区域四核苷酸重复多态性与重度肥胖患者高血压之间无关联。
J Endocrinol Invest. 2006 Oct;29(9):776-80. doi: 10.1007/BF03347370.
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A rare variant of the leptin gene has large effects on blood pressure and carotid intima-medial thickness: a study of 1428 individuals in 248 families.
埃及肥胖个体中瘦素基因四核苷酸重复多态性
Int J Health Sci (Qassim). 2015 Jan;9(1):63-71.
瘦素基因的一种罕见变异对血压和颈动脉内膜中层厚度有重大影响:对248个家庭中的1428名个体的研究。
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PREVALENCE OF CHRONIC DISEASES AND DISTRIBUTION OF SELECTED PHYSIOLOGIC VARIABLES IN A TOTAL COMMUNITY, TECUMSEH, MICHIGAN.密歇根州蒂康西一个完整社区的慢性病患病率及选定生理变量分布情况
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