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中国儿童中高血压相关单核苷酸多态性rs11191548与高密度脂蛋白胆固醇及瘦素的相关性

Associations of the hypertension-related single nucleotide polymorphism rs11191548 with high-density lipoprotein cholesterol and leptin in Chinese children.

作者信息

Wu Lijun, Gao Liwang, Zhao Xiaoyuan, Zhang Meixian, Wu Jianxin, Mi Jie

机构信息

Department of Epidemiology, Capital Institute of Pediatrics, No. 2 Yabao Road, Chaoyang District, Beijing, 100020, China.

Department of Biochemistry, Capital Institute of Pediatrics, No. 2 Yabao Road, Chaoyang District, Beijing, 100020, China.

出版信息

BMC Med Genet. 2018 Jan 16;19(1):9. doi: 10.1186/s12881-018-0523-y.

DOI:10.1186/s12881-018-0523-y
PMID:29338791
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5771196/
Abstract

BACKGROUND

The genome-wide association study has founded hypertension-related single nucleotide polymorphism (SNP) rs11191548 near CYP17A1 encoding a key enzyme involved in steroid metabolism, but the molecular mechanisms are not understood and the associations of the SNP with hypertension-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNP and two hypertension-related traits, lipids and leptin.

METHODS

We genotyped the SNP in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study.

RESULTS

The SNP rs11191548 was significantly associated with high-density lipoprotein cholesterol (HDL) (P = 0.014 and 0.028, respectively) and leptin (P = 0.011 and 0.026, respectively) under an additive model after adjustment for age, gender, and systolic blood pressure (SBP) or diastolic blood pressure (DBP). There was a statistically significant association of rs11191548 with high leptin after adjustment for age, gender, and SBP or DBP. The P-values remain significant after correction for multiple testing.

CONCLUSIONS

We demonstrate for the first time that the SNP rs11191548 near CYP17A1 is associated with HDL and leptin in Chinese children. These novel findings provide important evidence that HDL and leptin maybe possibly mediate the process of CYP17A1 involved in hypertension.

摘要

背景

全基因组关联研究发现,在编码参与类固醇代谢的关键酶的CYP17A1附近存在与高血压相关的单核苷酸多态性(SNP)rs11191548,但分子机制尚不清楚,且该SNP与高血压相关性状的关联尚未得到充分描述,尤其是在儿童中。本研究的目的是调查该SNP与两种高血压相关性状(血脂和瘦素)之间的关联。

方法

我们在北京儿童和青少年代谢综合征(BCAMS)研究中对该SNP进行了基因分型。共有3503名儿童参与了该研究。

结果

在对年龄、性别和收缩压(SBP)或舒张压(DBP)进行调整后,在加性模型下,SNP rs11191548与高密度脂蛋白胆固醇(HDL)(P分别为0.014和0.028)以及瘦素(P分别为0.011和0.026)显著相关。在对年龄、性别和SBP或DBP进行调整后,rs11191548与高瘦素之间存在统计学显著关联。在进行多重检验校正后,P值仍然显著。

结论

我们首次证明,CYP17A1附近的SNP rs11191548与中国儿童的HDL和瘦素相关。这些新发现提供了重要证据,表明HDL和瘦素可能介导了CYP17A1参与高血压的过程。

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本文引用的文献

1
The association between blood pressure and lipid levels in Europe: European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice.欧洲血压与血脂水平之间的关联:欧洲日常实践中心血管疾病风险预防与管理研究
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Circulation. 2016 Jan 26;133(4):398-408. doi: 10.1161/CIRCULATIONAHA.115.017936. Epub 2015 Dec 15.
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Arterial hypertension in children.儿童动脉高血压
Curr Opin Cardiol. 2015 Jul;30(4):403-10. doi: 10.1097/HCO.0000000000000191.
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Genetic and molecular aspects of hypertension.高血压的遗传与分子基础。
Circ Res. 2015 Mar 13;116(6):937-59. doi: 10.1161/CIRCRESAHA.116.303647.
7
Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension.在中国人群中进行的全基因组关联研究确定了血压和高血压的新基因座。
Hum Mol Genet. 2015 Feb 1;24(3):865-74. doi: 10.1093/hmg/ddu478. Epub 2014 Sep 23.
8
High-circulating leptin levels are associated with increased blood pressure in uncontrolled resistant hypertension.高循环瘦素水平与未控制的耐药性高血压中的血压升高有关。
J Hum Hypertens. 2013 Apr;27(4):225-30. doi: 10.1038/jhh.2012.29. Epub 2012 Jul 19.
9
A sex-specific effect of the CYP17A1 SNP rs11191548 on blood pressure in Chinese children.CYP17A1 SNP rs11191548 在中国儿童血压中存在性别特异性效应。
J Hum Hypertens. 2012 Dec;26(12):731-6. doi: 10.1038/jhh.2011.96. Epub 2011 Nov 3.
10
Common variants in or near FGF5, CYP17A1 and MTHFR genes are associated with blood pressure and hypertension in Chinese Hans.常见变异位于 FGF5、CYP17A1 和 MTHFR 基因内或附近,与中国汉族人群的血压和高血压有关。
J Hypertens. 2011 Jan;29(1):70-5. doi: 10.1097/HJH.0b013e32833f60ab.