AUTHOR=Zheng Peng-Fei , Yin Rui-Xing , Cao Xiao-Li , Chen Wu-Xian , Wu Jin-Zhen , Huang Feng 

TITLE=Effect of SYTL3-SLC22A3 Variants, Their Haplotypes, and G × E Interactions on Serum Lipid Levels and the Risk of Coronary Artery Disease and Ischaemic Stroke

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.713068

DOI=10.3389/fcvm.2021.713068

ISSN=2297-055X

ABSTRACT=<p><bold>Background:</bold> The current study aimed to investigate the effects of synaptotagmin-like 3 (<italic>SYTL3</italic>) and solute carrier family 22 member 3 (<italic>SLC22A3</italic>) 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.</p><p><bold>Methods:</bold> The genetic makeup of 6 <italic>SYTL3-SLC22A3</italic> SNPs in 2269 unrelated participants (controls, 755; CAD, 758 and IS, 756) of Chinese Han ethnicity was detected by the next-generation sequencing techniques.</p><p><bold>Results:</bold> The allele and genotype frequencies of the <italic>SYTL3</italic> rs2129209 and <italic>SLC22A3</italic> rs539298 SNPs were significantly different between the case and control groups. The <italic>SLC22A3</italic> 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 <italic>SLC22A3</italic> rs539298 SNP interacted with alcohol consumption reduced the risk of CAD and IS. The <italic>SYTL3</italic>-<italic>SLC22A3</italic> 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 <italic>SYTL3</italic>-<italic>SLC22A3</italic> 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/m<sup>2</sup> and cigarette smoking to affect serum lipid parameters such as triglyceride, high-density lipoprotein cholesterol, TC, and apolipoprotein A1 levels.</p><p><bold>Conclusions:</bold> Several <italic>SYTL3</italic>-<italic>SLC22A3</italic> 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.</p>