Wu Lijun, Gao Liwang, Zhao Xiaoyuan, Zhang Meixian, Wu Jianxin, Mi Jie
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.
BMC Med Genet. 2018 Jan 16;19(1):9. doi: 10.1186/s12881-018-0523-y.
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.
We genotyped the SNP in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study.
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.
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.
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。
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。
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。
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。