Abstract
Background: The current study aimed to investigate the effects of synaptotagmin-like 3 (SYTL3) and solute carrier family 22 member 3 (SLC22A3) single nucleotide polymorphisms (SNPs) and gene-environment (G × E) interactions on blood lipid levels as well as the risk of coronary artery disease (CAD) and ischaemic stroke (IS) in the Southern Chinese Han population.Methods: The genetic makeup of 6 SYTL3-SLC22A3 SNPs in 2269 unrelated participants (controls, 755; CAD, 758 and IS, 756) of Chinese Han ethnicity was detected by the next-generation sequencing techniques.Results: The allele and genotype frequencies of the SYTL3 rs2129209 and SLC22A3 rs539298 SNPs were significantly different between the case and control groups. The SLC22A3 rs539298 SNP was correlated with total cholesterol (TC) levels in controls, the rs539298G allele carriers maintained lower TC levels than the rs539298G allele non-carriers. At the same time, the SLC22A3 rs539298 SNP interacted with alcohol consumption reduced the risk of CAD and IS. The SYTL3-SLC22A3 A-C-A-A-A-A, G-T-C-G-C-A and A-T-A-A-C-A haplotypes increased and the A-C-A-A-C-G haplotype reduced the risk of CAD, whereas the SYTL3-SLC22A3 A-C-A-A-A-A, G-T-C-G-A-G and A-T-A-A-C-A haplotypes increased and the A-C-A-A-A-G and A-C-A-A-C-G haplotypes reduced the risk of IS. In addition, several SNPs interacted with alcohol consumption, body mass index ≥ 24 kg/m2 and cigarette smoking to affect serum lipid parameters such as triglyceride, high-density lipoprotein cholesterol, TC, and apolipoprotein A1 levels.Conclusions: Several SYTL3-SLC22A3 variants, especially the rs539298 SNP, several haplotypes, and G × E interactions, were related to blood lipid parameters and the risk of CAD and IS in the Southern Chinese Han population.
Highlights
Ischaemic cardiovascular and cerebrovascular diseases, including coronary artery disease (CAD) and ischaemic stroke (IS), are the primary contributors to global disability and death despite the vast therapeutic and diagnostic methods innovated in the last 10 years
We found that the rs539298G allele carriers had lower risk of CAD and IS than the rs539298G allele non-carriers. These findings suggested that the solute carrier family 22 member 3 (SLC22A3) rs539298A allele may be a genetic risk factor for ischaemic cardiovascular and cerebrovascular diseases, and the SLC22A3 rs539298G allele may reduce the risk of CAD and IS by affecting serum total cholesterol (TC) levels
The current research showed that the allelic and genotypic frequencies of the SLC22A3 rs539298 single nucleotide polymorphisms (SNP) were significantly different between controls and CAD/IS patients
Summary
Ischaemic cardiovascular and cerebrovascular diseases, including coronary artery disease (CAD) and ischaemic stroke (IS), are the primary contributors to global disability and death despite the vast therapeutic and diagnostic methods innovated in the last 10 years. Many genes and genetic loci associated with CAD [12] or IS [13] have been identified and reported in previous genomewide association studies (GWASes). A large number of genes or loci associated with lipid metabolism have been associated with CAD and/or IS [1,2,3]. Several compelling genes closely associated with blood lipid parameters, including synaptotagmin-like 3 (SYTL3) and solute carrier family 22-member 3 (SLC22A3), have been identified in the European population by GWASes [14]. The current study aimed to investigate the effects of synaptotagmin-like 3 (SYTL3) and solute carrier family 22 member 3 (SLC22A3) single nucleotide polymorphisms (SNPs) and gene-environment (G × E) interactions on blood lipid levels as well as the risk of coronary artery disease (CAD) and ischaemic stroke (IS) in the Southern Chinese Han population
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