Oncotarget

Research Papers:

Association study of IGFBP1 and IGFBP3 polymorphisms with hypertension and cardio-cerebral vascular diseases in a Chinese Han population

Zhengmei Fang, Song Yang, Lijun Zhu, Ying Li, Yanchun Chen, Yuelong Jin, Xianghai Zhao, Hailong Zhao, Xiaotian Chen, Yanping Zhao, Chong Shen _ and Yingshui Yao

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Oncotarget. 2017; 8:77836-77845. https://doi.org/10.18632/oncotarget.20839

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Abstract

Zhengmei Fang1,*, Song Yang2,*, Lijun Zhu1, Ying Li3, Yanchun Chen2, Yuelong Jin1, Xianghai Zhao2, Hailong Zhao4, Xiaotian Chen3, Yanping Zhao5, Chong Shen3 and Yingshui Yao1

1Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, Wuhu 241001, China

2Department of Cardiology, Affiliated Yixing People’s Hospital of Jiangsu University, People’s Hospital of Yixing City, Yixing 214200, China

3Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China

4Central Laboratory, Affiliated Yixing People’s Hospital of Jiangsu University, People’s Hospital of Yixing City, Yixing 214200, China

5Department of Neurology, Affiliated Yixing People’s Hospital of Jiangsu University, People’s Hospital of Yixing City, Yixing 214200, China

*These authors have contributed equally to this work

Correspondence to:

Chong Shen, email: [email protected]

Yingshui Yao, email: [email protected]

Keywords: hypertension, IGFBP1, IGFBP3, cardio-cerebral vascular disease, polymorphisms

Received: March 26, 2017    Accepted: August 17, 2017    Published: September 12, 2017

ABSTRACT

Previous studies have showed that insulin-like growth factor (IGF) axis is involved in the development of hypertension. It is unclear whether genetic variants in the IGF-binding proteins (IGFBPs) contribute to the susceptibility to hypertension. Three single-nucleotide polymorphisms (SNPs) in IGFBP1 and four SNPs in IGFBP3 were selected for genotyping in 2,012 hypertension cases and 2,210 healthy controls and 4,128 subjects were followed up for a median of 5.01 years. Multiple logistic regression and Cox regression were performed to evaluate the association of these seven SNPs with hypertension and cardio-cerebral vascular disease (CCVD). In the case-control study, rs2132572 and rs3110697 at IGFBP3 were significantly associated with hypertension, and the odds ratios (ORs) of rs2132572 (CT+TT vs. CC) and rs3110697 (GA+AA vs. GG) were 1.235 (P=0.002) and 1.176 (P=0.013), respectively (PFDR<0.05). The association of rs2132572 (TT vs. CT+CC) with hypertension was further replicated in the follow-up population, with a hazard ratio (HR) of 1.694 (P=0.014). rs1874479 at IGFBP1 was significantly associated with CCVD, particularly with stroke, and the HRs of the additive model were 1.310 (P=0.007) and 1.372 (P=0.015). Moreover, the hypertension cases presented with lower serum IGFBP1 levels than the controls (P=0.011). The serum levels of IGFBP1 significantly varied among the genotypes of rs1065780, rs2854843 and rs13223993, both in the controls and in the hypertension cases (P<0.05). These findings suggest that the genetic variants of IGFBP1 and IGFBP3 were associated with an increased risk of stroke and hypertension, respectively. Lower serum IGFBP1 levels may predict an increased risk of hypertension.


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