Elsevier

Gene

Volume 512, Issue 1, 1 January 2013, Pages 41-46
Gene

Methods Paper
Association study of CRP gene polymorphism and hypertension in Han Chinese population

https://doi.org/10.1016/j.gene.2012.09.107Get rights and content

Abstract

Background

Serum C-reactive protein (CRP) and genetic variation of CRP gene have been reported as a strong, independent predictor of myocardial infarction and stroke. But there is rare association evidence of CRP genetic variation and hypertension (HT).

Methods

A community-based case–control study including 1331 cases with HT and 1400 controls was used to evaluate the association of tagSNPs covered CRP gene, CRPP1 gene and 40 kb upstream with HT in a Chinese Han population. Haplotypes and stratification analysis were applied to further evaluate relationships between the screened SNPs and HT and general linear model (GLM) was applied to compare blood pressure levels between genotypes.

Results

In stage 1, five SNPs had positive association with HT (P < 0.05) and entered stage 2 and two SNPs rs876537 and rs10737175 polymorphisms showed significant association with HT in joint sample. Haplotype analysis showed that comparing with common haplotype T–C which was constructed by rs6677719 and rs10737175, haplotype T–T significantly associated with HT after adjusted covariates. Stratification analysis found significant associations of HT for rs876537, rs2808630, rs6677719 and rs10737175 in ≥ 50 years group, rs876537, rs10737175 in female, rs876537 and rs10737175 in non-smoking and non-drinking populations as well as rs2808630 in non-drinking population. Furthermore, quantitative trait analysis indicated significant differences of SBP and DBP between the genotypes of rs10737175, rs876537 and rs2808630 in non-treatment hypertensive cases and control population.

Conclusions

The findings of this study support that CRP gene polymorphisms have significant association with genetic susceptibility of HT and quantitative traits of blood pressure.

Highlights

► TagSNPs covered CRP gene, CRPP1 gene and 40 kb upstream were assessed for HT. ► SNPs rs876537 and rs10737175 of CRP gene had major effect on hypertension. ► Haplotype T–T structured of rs6677719 and rs10737175 had joint effect on HT. ► Age and sex might modify genetic effect of CRP gene on HT. ► rs10737175, rs2808630 and rs876537 are positively associated with BP elevation.

Introduction

As the leading risk factor for stroke and heart disease throughout the world, essential hypertension (HT) is a complex quantitative trait that is affected by varying combinations of genetic and environmental factors (Staessen et al., 2003, Zacchigna et al., 2006). A large number of genes are potentially involved in blood pressure regulation and even the susceptibility to hypertension (Bao et al., 2005). Recently, several studies proved that arterial inflammation plays a key role in the development of atherosclerosis involved in cardiovascular disorders (Elkind et al., 2010, Woollard and Geissmann, 2010).

C-reactive protein (CRP) is an acute phase protein often presented in the atherosclerotic lesion and its concentration in serum reflects the inflammatory condition of the patient (Masia et al., 2007, Paffen and DeMaat, 2006). CRP continually elevating in the acute-phase has proven to be a sensitive systemic marker of inflammation and the endothelial inflammatory response involved in the initiation and progression of atherosclerosis (Chamarthi et al., 2011, Genest, 2010, Paffen and DeMaat, 2006). Probably, impaired arterial elasticity would contribute to blood pressure elevation and hypertension.

A study of animal model showed that adeno-associated virus-green fluorescent protein vector-mediated CRP expression resulted in hypertension mediated through reduced serum nitric oxide (NO) production and subsequent alteration in serum endothelin 1 (ET-1) and renin–angiotensin system activation (Guan et al., 2009). Furthermore, our previous study found that high sensitive CRP (hsCRP) elevation (≥ 3.0 mg/L) has potential as a risk marker of future cardiovascular disease as well as hypertension in North Chinese population (Wu et al., 2012). These results indicated a causal role for CRP in the pathogenesis of hypertension. CRP is encoded by CRP gene and the variants on the gene might regulate CRP expression. Zacho et al. (2008) reported that several single nucleoside polymorphisms (SNPs) in the CRP gene had significantly joint effect on marked increases in CRP levels and Komurcu-Bayrak et al. (2009) further replicated that two haplotypes structured of four SNPs of CRP gene had a joint effect on serum CRP levels and the susceptibility to hypertension. These findings would warrant broader insight into susceptible genetic variations of CRP gene as well as region nearby and thereby mechanisms leading to blood pressure elevation and hypertension.

In the present study, a case–control study was conducted to investigate the association of common variants of relative long region covered CRP gene, the C-reactive protein pseudogene 1 (CRPP1) genes and 5′ upstream 40 kb sequences with HT in a South Han Chinese population.

Section snippets

Subjects

In this study, hypertensive cases and controls were recruited from a rural population in Jiangsu province by an epidemiological stratification sampling approach as previous reported (Yang et al., 2012) .1331 cases aged 20 to 62 years were included for systolic blood pressure (SBP)  140 mm Hg, and/or diastolic blood pressure (DBP)  90 mm Hg, or currently administering antihypertensive medication. Subjects with a clinical history of secondary hypertension, coronary heart disease, kidney disease and

Clinical characteristics

The characteristics of subjects included in the stage 1, stage 2 and joint analysis were listed in Table 1. There were no significant differences of age, proportions of men, smoking and drinking status between cases and controls in stage 1, stage 2 and main sample. As expected, the cases generally had higher SBP and DBP, BMI, TC, TG, LDL-C and GLU levels and lower HDL-C than that in controls. Both SBP and DBP in stage 1 were a little lower than that of stage 2 (P < 0.05).

Association analyses

Six SNPs in controls were

Discussion

Large-scale prospective studies show that the inflammatory biomarker CRP is an independent predictor of future cardiovascular events and support for a role of CRP in the pathogenesis of atherosclerosis (Danesh et al., 2004, Levy et al., 2001, Ridker, 2007). More recently, some intensive searches have been initiated for targeted vascular anti-inflammatory agents that might have efficacy in the prevention and treatment of coronary and cerebral disease although there is ongoing debate regarding

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant no. 81273165, grant no. 30800947 and grant no. 81072367), Health Research Program of Jiangsu Province (grant no. H200839), Science & Technology Program of Jiangsu Province (grant no. BE2009681), Key Science & Technology Program of Jiangsu Province (grant no. BE2009613), the Natural Science Foundation of Jiangsu Province (grant no. BK2011776) and the Priority Academic Program for the Development of Jiangsu Higher

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  • Cited by (5)

    Yanping Zhao, Hairu Wang and Sijun Liu equally contributed to this work.

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