Abstract

Objective: NINJ2 regulates activation of vascular endothelial cells, and genome-wide association studies showed that variants in NINJ2 confer risk to stroke. However, whether variants in NINJ2 are associated with coronary artery disease (CAD) is unknown.Methods: We genotyped rs34166160 in NINJ2 in two independent Chinese GeneID populations which included 2,794 CAD cases and 4,131 controls, and performed genetics association studies. Functional studies were also performed to reveal the mechanisms.Results: Allele rs34166160 significantly confers risk to CAD in the GeneID Hubei population which contained 1,440 CAD cases and 2,660 CAD-free controls (observed P-obs = 6.39 × 10−3 with an odds ratio (OR) was 3.39, adjusted P-adj = 8.12 × 10−3 with an OR of 3.10). The association was replicated in another population, GeneID Shandong population contained 1,354 CAD cases and 1,471 controls (P-obs = 3.33 × 10−3 with an OR of 3.14, P-adj = 0.01 with an OR of 2.74). After combining the two populations, the association was more significant (P-obs = 1.57 × 10−5 with an OR of 3.58, P-adj = 3.41 × 10−4 with an OR of 2.80). In addition, we found that rs34166160 was associated with the mRNA expression level of NINJ2 and the flanking region of rs34166160 can directly bind with transcriptional factor CCAAT-box/enhancer-binding protein beta, and the risk A allele has more transcription activity than non-risk C allele with or without LPS in HUVEC cells.Conclusions: Our study demonstrates that the functional rare variant rs34166160 in NINJ2 confers risk to CAD for the first time, and these findings further expand the range of the pathology of CAD and atherosclerosis.

Highlights

  • Atherosclerosis is the leading pathological cause of coronary heart disease (CAD) and ischemic stroke, which claims about 14 million of lives every year and is the main cause of mortality and morbidity worldwide [1, 2]

  • The siRNA approach was used to knockdown the expression of C/EBP beta in Human Umbilical Vein Endothelial Cells (HUVEC), and the results showed that compared to controls, expression of NINJ2 was decreased by knocking down the expression of C/EBP beta in HUVEC (p < 0.05) (Figure 2B)

  • Our results demonstrated that the minor A allele of a rare variant, rs34166160, in the NINJ2 gene was conferring risk to CAD in both two independent populations (Table 2)

Read more

Summary

Introduction

Atherosclerosis is the leading pathological cause of coronary heart disease (CAD) and ischemic stroke, which claims about 14 million of lives every year and is the main cause of mortality and morbidity worldwide [1, 2]. Atherosclerosis is a complex trait caused by environmental factors, genetic factors, and their interactions [3]. Risk factors such as abnormal lipid concentrations, obesity, diabetes, smoking, hypertension, physical inactivity, psychosocial situations, and alcohol intake are shared among CAD and ischemic stroke [4, 5]. Identification of novel genetic risk variants that are shared by both ischemic stroke and CAD may identify the underlying pathophysiology of atherosclerosis, and facilitate diagnosis, which may lead to prevention and treatment of ischemic stroke and CAD

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call