Abstract
BackgroundAbnormal lipid concentrations are risk factors for atherosclerosis and cardiovascular disease. The pathological susceptibility to cardiovascular disease risks such as metabolic syndrome, diabetes mellitus, hypertension, insulin resistance, and so on differs between Sasang constitutional types.MethodsWe used multiple regression analyses to study the association between lipid-related traits and genetic variants from several genome-wide association studies according to Sasang constitutional types, considering that the Tae-Eum (TE) has predominant cardiovascular risk.ResultsBy analyzing 26 variants of 20 loci in two Korean populations (8,597 subjects), we found that 12 and 5 variants, respectively, were replicably associated with lipid levels and dyslipidemia risk. By analyzing TE and non-TE type (each 2,664 subjects) populations classified on the basis of Sasang constitutional medicine, we found that the minor allele effects of three variants enriched in TE type had a harmful influence on lipid risk (near apolipoprotein A-V (APOA5)-APOA4-APOC3-APOA1 on increased triglyceride: p = 8.90 × 10-11, in APOE-APOC1-APOC4 on increased low-density lipoprotein cholesterol: p = 1.63 × 10-5, and near endothelial lipase gene on decreased high-density lipoprotein cholesterol: p = 4.28 × 10-3), whereas those of three variants (near angiopoietin-like 3 gene, APOA5-APOA4-APOC3-APOA1, and near lipoprotein lipase gene on triglyceride and high-density lipoprotein cholesterol) associated in non-TE type had neutral influences because of a compensating effect.ConclusionsThese results implied that the minor allele effects of lipid-associated variants may predispose TE type subjects to high cardiovascular disease risk because of their genetic susceptibility to lipid-related disorders.
Highlights
Abnormal lipid concentrations are risk factors for atherosclerosis and cardiovascular disease
Common variants primarily associated with low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and TG belong to the following loci: ABCG5, ABCG8, SORT1, DNAH11, HMGCR, HNF1A, LDLR, MAFB, PCSK9, and TIMD4-HAVCR1; ATP-binding cassette transporter A1 (ABCA1), ANGPTL4, CETP, GALN2, HNF4A, LCAT, Endothelial lipase (LIPG), MADD-FOLH1, MVK-MMAB, and TTC39B; and Angiopoietin-like 3 (ANGPTL3), GCKR, MLXIPL, TRIB1, and XKR6-AMAC1L2, respectively
The TE type subjects presented relatively higher body mass index (BMI), waist circumference, blood pressures, glucose level, and lipid parameters such as LDLC, HDLC, and TG, as well as cardiovascular risk factors such as dyslipidemia than those found in NTE type subjects; these findings were consistent with those of previous reports [4,10,11,12,13,27]
Summary
Abnormal lipid concentrations are risk factors for atherosclerosis and cardiovascular disease. The pathological susceptibility to cardiovascular disease risks such as metabolic syndrome, diabetes mellitus, hypertension, insulin resistance, and so on differs between Sasang constitutional types. Dyslipidemia is characterized by abnormal levels of lipids, including low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and triglycerides (TG), in the bloodstream. Sasang constitutional medicine classified human beings into 4 groups on the basis of distinctive physical, physiological, and psychological characteristics as constitutional diabetes mellitus, hypertension, and insulin resistance, differs between TE and the other types [2,10,11,12,13]. Several research groups have analyzed the results of genome-wide association studies (GWAS) and replication studies and reported several single nucleotide polymorphisms (SNPs) that affect blood lipid levels and are risk factors for cardiovascular disease [16,17,18,19]. Some loci associated with TG are simultaneously related to the loci associated with HDLC (5 loci: APOA5-APOA4-APOC3APOA1, FADS1-FADS2-FADS3, LIPC, LPL, and PLTP) or LDLC (3 loci: APOB, APOE-APOC clusters, and NCAN)
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