BRD4 and PIN1 gene polymorphisms are associated with high pulse pressure risk in a southeastern Chinese population

Jin-Jia Qiu,Kai Zeng,Ying-Yi Lin,Na Zhang,Yi-Jie Tang,Rui-Zhi Yang,Xiao-Dan Wu,Hong-Da Cai,Min Liang,Hao-Jie Xu

doi:10.1186/s12872-020-01757-x

Abstract

BackgroundBRD4 and PIN1 have been described to be involved in inflammation and vascular endothelial cell dysfunction, which in turn may increase pulse pressure.HypothesisGenetic mutations within the BRD4 and PIN1 genes could affect the risk of high pulse pressure.MethodsA total of four single nucleotide polymorphisms (SNPs) (BRD4: rs4808278; PIN1: rs2233678, rs2287838, and rs2233682) were genotyped in a cohort of 666 hypertensive patients and 232 normotensive controls with Chinese Han origin. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among the four SNPs within the BRD4 and PIN1 genes and diabetes. Logistic regression analysis was performed to calculate the odds ratio (ORs) (95% confidence interval (CI)) for the association between the four SNPs.ResultsAdjusted for age, weight, waist circumference, drinking, smoking, hypertension, and diabetes, high pulse pressure risk was significantly higher for carriers with the rs4808278-TT genotype in BRD4 than those with wild genotypes (OR: 0.400, 95% CI: 0.217–0.737, P* < 0.05). However, we did not find any significant association of rs2233678, rs2287838, and rs2233682 in PIN1 with high pulse pressure susceptibility after covariate adjustment. GMDR analysis indicated a significant three-locus model (P = 0.0107) involving rs4808278, rs2233678, and diabetes, the cross-validation consistency of the three-locus models was 9/10, and the testing accuracy was 57.47%.ConclusionsGenetic mutations within BRD4 (rs4808278) could affect the susceptibility to high pulse pressure in a southeastern Chinese population.

Highlights

BRD4 and PIN1 have been described to be involved in inflammation and vascular endothelial cell dys‐ function, which in turn may increase pulse pressure.Hypothesis: Genetic mutations within the BRD4 and PIN1 genes could affect the risk of high pulse pressure
It is possible that variants in BRD4 and PIN1 genes may lead to decreased vascular elasticity by destroying endothelial cells and causing atherosclerosis
Older subjects with higher levels of body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), obesity, diabetes, and smoking had a high risk of high Pulse pressure (PP) (P < 0.001)

Summary

Introduction

BRD4 and PIN1 have been described to be involved in inflammation and vascular endothelial cell dys‐ function, which in turn may increase pulse pressure. Hypothesis: Genetic mutations within the BRD4 and PIN1 genes could affect the risk of high pulse pressure. The decrease in vascular elasticity is an important factor for the increase in pulse differential pressure and may result from inflammation and vascular endothelial. A previous study has reported that BRD4 and PIN1 are involved in inflammation and vascular endothelial cell dysfunction. Inhibiting Brd and Pin expression alleviates enhancermediated inflammatory transcription and atherosclerosis, which indicates that BRD4 and PIN1 play a vital role in the development of vascular inflammation and atherosclerosis [10,11,12,13]. It is possible that variants in BRD4 and PIN1 genes may lead to decreased vascular elasticity by destroying endothelial cells and causing atherosclerosis

Objectives

Methods

Results

Conclusion