We assessed the associations between the APOA5  −1131T>C polymorphism and lipid parameters and other risk factors of the metabolic syndrome in Korean subjects. A total of 2,901 participants from 20 oriental medical hospitals in Korea were enrolled between 2006 and 2011. According to the modified National Cholesterol Education Program Adult Treatment Panel III definitions, subjects were classified into the metabolic syndrome group and control group. The APOA5  −1131T>C genotype was significantly associated with serum high-density lipoprotein cholesterol levels (effect = − 1.700 mg/dL, P=6.550-E07) in the total study population after adjustment for differences in age and gender. The association of the APOA5  −1131T>C genotype with serum log-transformed triglyceride was also significant in an additive genetic model (effect = 0.056 mg/dL, P=2.286E-19). After adjustment for age and gender, we determined that the odds ratio for the occurrence of the metabolic syndrome was 1.322 for C-allele carriers in the additive model (95% CI = [1.165 − 1.501], P=1.48E-05). In the current study, we demonstrated that the APOA5  −1131T>C polymorphism is associated with the metabolic syndrome because of its remarkable effect on serum triglyceride levels in Korean subjects.

Obesity and osteoporosis share common physiological factors, including the presence of atherosclerosis, a risk factor for cardiometabolic disease, as well as a common progenitor that differentiates into both adipocytes and osteoblasts. Among the 23 polymorphisms associated with bone mineral density (BMD) in recent genome-wide association studies (GWASs), an Osterix polymorphism has been identified and associated with childhood obesity in girls. Therefore, we focused on elucidating polymorphisms associated with adulthood obesity in a sex-dependent manner among the previously published BMD-associated polymorphisms from GWASs. We performed 2 screenings of 18 BMD-associated polymorphisms for obesity-related traits in 2,362 adults aged >20 years. We excluded 13 polymorphisms showing deviations from Hardy–Weinberg equilibrium or no association with obesity-related traits (body mass index, waist circumference (WC), and waist-to-hip ratio). Among 5 selected polymorphisms (rs9594738 of RANKL, rs17066364 of NUFIP1, rs7227401 of OSBPL1A, and rs1856057 and rs2982573 of ESR1) analyzed, 2 polymorphisms (rs9594738 and rs17066364) were associated with obesity-related traits. We found sex-dependent associations such that the 4 polymorphisms (excluding rs9594738 of RANKL) were associated with abdominal traits such as WC and waist-to-hip ratio only in men. In addition, when the combined genetic risk score (GRS) for WC increase was calculated with 4 SNPs (rs9594738, rs17066364, rs7227401, and rs1856057) exhibiting similar trends for both sexes, the magnitude of the GRS effect for the WC increase was larger in men than in women (effect size = 0.856 cm, P = 0.0000452 for men; effect size = 0.598 cm, P = 0.00228 for women). In summary, we found 4 polymorphisms, previously related to osteoporosis, to be associated to obesity-related traits in a sex-dependent manner in Korean adults, particularly in men.

BackgroundBody constitutional types described in the traditional Korean medicine system, Sasang constitutional medicine, are heritable, as has been revealed by twin and family studies. Thus, individuals with the same constitution type usually have similar pathophysiological and psychological traits. In several recent genome-wide association (GWA) analyses performed to identify constitution-associated variants, the association signals were not replicated due to small sample size and dissimilar, non-objective methods for classification of the constitutional types.MethodsWe conducted GWA analysis and followed replication analysis in two large populations (5,490 subjects: 3,810 subjects at discovery stage and 1,680 subjects at replication stage) to identify the replicable constitution-associated variants, wherein subjects with the highest tertile of constitution probability values versus the reference with the lowest tertile of the values obtained from a recently developed constitution analysis tool were compared.ResultsWe found that the obesity-risk variant in intron 1 of the fat mass and obesity–associated (FTO) gene was replicably inversely associated with the So-Eum (SE) type, characterized by reduced appetite, slim body, and cautious personality (rs7193144 in combined samples: odds ratio = 0.729, p = 1.47 × 10−7), and substantial association signal remained after controlling for body mass index (BMI). In contrast, the association of the variant with the Tae-Eum type, characterized by high body mass, disappeared after controlling BMI.ConclusionsIn summary, the obesity-risk variant in FTO intron 1 was inversely associated with the SE type, independent of BMI, which corresponded well with the characteristics of the SE type, such as the lowest body mass and lowest susceptibility to metabolic disorders among the constitutional types. Therefore, the obesity-risk variant of FTO associated with body mass increase might be involved in the determination of body constitution type.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-015-0609-4) contains supplementary material, which is available to authorized users.

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.

BackgroundSingle-nucleotide polymorphisms (SNPs) around the apolipoprotein A5 gene (APOA5) have pleiotropic effects on the levels of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C). APOA5 SNPs have also been associated with metabolic syndrome (MS). Here, we constructed haplotypes with SNPs spanning APOA5 and ZNF259, which are approximately 1.3 kb apart, to perform association analyses with the risk for MS and the levels of TG and HDL-C in terms of a TG:HDL-C ratio.MethodsThe effects of three constructed haplotypes (TAA, CGG, and CGA, in the order of rs662799, rs651821, and rs6589566) on the TG:HDL-C ratio and MS were estimated using multiple regression analyses in 2,949 Koreans and in each gender separately (1,082 men and 1,867 women).ResultsThe haplotypes, CGG and CGA, were associated with the TG:HDL-C ratio and the risk of MS development in both genders. That is, the minor alleles of the rs662799 and rs651821 in APOA5, irrespective of which allele was present at rs6589566, had the marked effects. Interestingly, a C–G–A haplotype at these three SNPs had the most marked effects on the TG:HDL-C ratio and the risk of MS development in women.ConclusionsWe have identified the novel APOA5-ZNF259 haplotype manifesting sex-dependent effects on elevation of the TG:HDL-C ratio as well as the increased risk for MS.