TRIB1 and TRPS1 variants, G\u2009\xd7\u2009G and G\u2009\xd7\u2009E interactions on serum lipid levels, the risk of coronary heart disease and ischemic stroke

Qing-Hui Zhang,Xiao-Li Cao,Jin-Zhen Wu,Wu-Xian Chen,Rui-Xing Yin

doi:10.1038/s41598-019-38765-7

Abstract

This study aimed to assess the association of the tribbles pseudokinase 1 (TRIB1) and transcriptional repressor GATA binding 1 (TRPS1) single nucleotide polymorphisms (SNPs) and the gene-gene (G × G) and gene-environment (G × E) interactions with serum lipid levels, the risk of coronary heart disease (CHD) and ischemic stroke (IS) in the Guangxi Han population. Genotyping of the rs2954029, rs2980880, rs10808546, rs231150, rs2737229 and rs10505248 SNPs was performed in 625 controls and 1146 unrelated patients (CHD, 593 and IS, 553). The genotypic and allelic frequencies of some SNPs were different between controls and patients (CHD, rs2954029 and rs231150; IS, rs2954029 and rs2980880; P < 0.05-0.01). Two SNPs were associated with increased risk of CHD (rs2954029 and rs231150) and IS (rs2954029) in different genetic models. Several SNPs in controls were associated with total cholesterol (rs2954029, rs2980880 and rs2737229), triglyceride (rs2954029 and rs10808546), low-density lipoprotein cholesterol (rs2954029), high-density lipoprotein cholesterol (rs2980880 and rs231150) and apolipoprotein A1 (rs2737229) levels. The rs2954029TA/AA-age (>60 year) interaction increased the risk of CHD, whereas the rs10808546CT/TT-drinking interaction decreased the risk of IS. The rs2954029A-rs2980880C-rs10808546C haplotype was associated with increased risk of CHD and IS. The rs2954029A-rs2980880T-rs10808546C haplotype was associated with increased risk of CHD. The rs2954029-rs231150 interactions had an increased risk of both CHD and IS. These results suggest that several TRIB1 and TRPS1 SNPs were associated with dyslipidemia and increased risk of CHD and IS in our study population. The G × G and G × E interactions on serum lipid levels, and the risk of CHD and IS were also observed.

Highlights

Coronary heart disease (CHD) and ischemic stroke (IS) remain the leading causes of morbidity and mortality worldwide[1,2], resulting in a substantial economic and social burden[3]
The values of body mass index (BMI), systolic blood pressure, pulse pressure, and triglyceride (TG) were higher but serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A1, the percentages of subjects who consumed alcohol, and the ratio of ApoA1 to ApoB were lower in coronary heart disease (CHD) patients than in controls (P < 0.001 for all)
Several single nucleotide polymorphisms (SNPs) were associated with TC, TG, low-density lipoprotein cholesterol (LDL-C, rs2954029), HDL-C and ApoA1

Summary

Introduction

Coronary heart disease (CHD) and ischemic stroke (IS) remain the leading causes of morbidity and mortality worldwide[1,2], resulting in a substantial economic and social burden[3]. Many genes and loci in previous genome-wide association studies (GWASes) have been shown to be predisposed to CHD8 or IS9 in different populations. Parameter Number Male/female Age, years Body mass index, kg/m2 Systolic blood pressure, mmHg Diastolic blood pressure, mmHg Pulse pressure, mmHg Cigarette smoking, n (%) Alcohol consumption, n (%) Total cholesterol, mmol/L Triglyceride, mmol/L HDL-C, mmol/L LDL-C, mmol/L Apolipoprotein (Apo) A1, g/L ApoB, g/L ApoA1/ApoB been significantly associated with multiple plasma lipid traits and cardiovascular disease in different populations. Using the method of tag SNPs combined with recent research reports, we detected six SNPs in the TRIB1 (rs2954029, rs2980880 and rs10808854) and TRPS1 (rs231150, rs2737229 and rs10505248), their G × G and G × E interactions on serum lipid levels, the risk of CHD and IS in a Southern Chinese Han population

Objectives

Methods

Results

Conclusion