Abstract
Little is known about the association of the TIMD4 (T-cell immunoglobulin and mucin domain 4 gene)-HAVCR1 (hepatitis A virus cellular receptor 1) variants and lipid metabolism, the risk of coronary heart disease (CHD) and ischemic stroke (IS). The present study aimed to determine the TIMD4-HAVCR1 variants, their haplotypes and gene–environment interactions on serum lipid levels, the risk of CHD and IS, and the lipid-lowering efficacy of atorvastatin in a southern Chinese Han population. Genotypes of three variants in 622 controls, 579 CHD, and 546 IS patients were determined by the Snapshot technology. Atorvastatin calcium tablet (20 mg/day) was given in 724 hyperlipidemic patients for 8 weeks after genotyping. The rs12522248 genotypic and allelic frequencies were different between controls and patients, and were associated with the risk of CHD and IS. The rs1501908G-rs12522248T-rs2036402T haplotype was associated with an increased risk of CHD; the G-C-T haplotype was associated with lower risk of CHD; and the C-C-C haplotype was associated with an increased risk of IS. Variants and their haplotypes in controls were associated with triglyceride (rs1501908), low-density lipoprotein cholesterol (LDL-C, rs1501908, G-T-T), high-density lipoprotein cholesterol (HDL-C, rs12522248, C-C-C) and the ratio of total cholesterol (TC) to HDL-C (C-C-C). Interactions of rs1501908- and rs2036402-alcohol (HDL-C); rs1501908- and rs12522248-high body mass index (hBMI, ≥24 kg/m2; TC); and TIMD4-HAVCR1 variants-atorvastatin on several lipid parameters were detected. Interactions of rs12522248TC/CC-hBMI, G-T-T-, and C-C-C-smoking on the risk of CHD; and C-C-C-smoking, C-C-C-, and G-C-T-hBMI on the risk of IS were also observed. These findings suggest that the TIMD4-HAVCR1 variants may be the genetic risk factors for CHD and IS.
Highlights
Coronary heart disease (CHD) and ischemic stroke (IS) remain the leading causes of morbidity and mortality globally [1,2]
The present study showed that the genotypic and allelic frequencies of the rs12522248 single nucleotide polymorphism (SNP) were different between controls and CHD or IS patients, and the rs12522248 genotypes or alleles were associated with the risk of CHD and IS in different genetic models
We showed that the genotypic and allelic frequencies of the rs12522248 SNP were different between controls and patients, and the genotypes of the rs12522248 SNP were associated with the risk of CHD and c 2018 The Author(s)
Summary
Coronary heart disease (CHD) and ischemic stroke (IS) remain the leading causes of morbidity and mortality globally [1,2]. ApoA1 is a serious risk factor for atherosclerotic vascular diseases [5,6,7,8,9,10] Both blood lipid disorder and atherosclerotic disease are multifactorial and complicated diseases caused by genetic factors [11,12], environmental factors [13,14,15,16], and their interactions c 2018 The Author(s).
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