Prediction of genetic risk for dyslipidemia

Abstract

The purpose of the present study was to identify genetic variants that confer susceptibility to dyslipidemia. A total of 5213 individuals from two independent populations were examined: Subject panel A comprised 3794 individuals who visited participating hospitals; subject panel B comprised 1419 community-dwelling elderly individuals. The genotypes for 100 polymorphisms of 65 candidate genes were determined. The chi(2) test and multivariable logistic regression analysis revealed that seven polymorphisms of APOA5, APOC3, APOA1, ACAT2, and LPL were significantly associated with hypertriglyceridemia, six polymorphisms of APOA5, LIPC, and CYP3A4 with low HDL-cholesterol, and three polymorphisms of APOE and CCR2 with high LDL-cholesterol in subject panel A. For validation of these associations, the same polymorphisms were examined in subject panel B. Six polymorphisms of APOA5, APOC3, APOA1, and LPL were again significantly associated with hypertriglyceridemia, three polymorphisms of APOA5 with low HDL-cholesterol, and two polymorphisms of APOE with high LDL-cholesterol. Serum triglyceride, HDL-cholesterol, and LDL-cholesterol concentrations differed significantly among genotypes of these corresponding polymorphisms in both subject panels. These results indicate that polymorphisms of APOA5, APOC3, APOA1, and LPL are determinants of hypertriglyceridemia and that those of APOA5 and APOE are determinants of low HDL-cholesterol and high LDL-cholesterol, respectively, in Japanese individuals.

Synergistic effects of genetic variants of APOA5 and BTN2A1 on dyslipidemia or metabolic syndrome

“…We previously showed that the -1131T→C polymorphism (rs662799) of the apolipoprotein A-V gene (APOA5) and the C→T polymorphism (rs6929846) of the butyrophilin, subfamily 2, member A1 gene (BTN2A1) were significantly associated with the prevalence of dyslipidemia (10,11) and MetS (12)(13)(14) in Japanese individuals. Given that gene-gene interactions may play important roles in the development of multifactorial complex disorders, we hypothesized that rs662799 of APOA5 and rs6929846 of BTN2A1 may synergistically affect the development of dyslipidemia and MetS.…”

Association of a polymorphism of BTN2A1 with dyslipidemia in East Asian populations

“…Blood samples were centrifuged at 1,600 x g for 15 min at 4˚C, and serum was separated and stored at -30˚C until analysis. The serum concentrations of triglycerides, high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol were measured as previously described (7).…”

Dyslipidemia: Genetics and Role in the Metabolic Syndrome

“…The human APOA5 gene is located on chromosome 11 (11q23) in the APOA1/C3/A4/A5 gene cluster. Several APOA5 SNPs have been associated with reduced HDL-C levels; and, perhaps, the most well studied and consistent associations have been observed for rs651821 and rs662799 (Table 1) (Grallert et al, 2007;Hubacek, 2005;Klos et al, 2006;Lai et al, 2003;Qi et al, 2007;Talmud et al, 2002a;Yamada et al, 2008;Yamada et al, 2007). Apolipoprotein C-3 (APOC3; APOC-III) is an inhibitor of LPL and is transferred to HDL during the hydrolysis of TG-rich lipoproteins (Kwan et al, 2007;Miller and Zhan, 2004).…”

“…The human HL/LIPC gene is located on chromosome 15 (15q21). Several HL/LIPC SNPs have been associated with HDL-C levels (Table 1) (Andersen et al, 2003;Costanza et al, 2005;de Andrade et al, 2004;Fang and Liu, 2002;Grarup et al, 2008;Iijima et al, 2008;Isaacs et al, 2007;Kathiresan et al, 2008b;Ko et al, 2004;McCaskie et al, 2006;Nettleton et al, 2007;Tai et al, 2003a;Talmud et al, 2002b;Whiting et al, 2005;Yamada et al, 2007). However, the most consistent associations have been observed for rs1800588 and rs2070895 and, several SNPs in the promoter region are in strong LD (Boes et al, 2009).…”