Abstract 3456: Assessment of Genetic Risk for Hypertriglyceridemia
Introduction. Hypertriglyceridemia is an important risk factor for coronary heart disease. The purpose of the present study was to identify gene polymorphisms associated with hypertriglyceridemia (serum triglyceride concentration, ≥1.65 mmol/L) for assessment of the genetic risk for this condition.
Methods. A total of 5206 individuals from two independent populations was examined: Subject panel A comprised 3787 individuals who either visited outpatient clinics of or were admitted to the participating hospitals because of various symptoms or for a health checkup; subject panel B comprised 1419 community-dwelling elderly individuals. The genotypes for 100 polymorphisms of 65 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Given the multiple comparisons of genotypes with hypertriglyceridemia, we adopted the criterion of a false discovery rate (FDR) of <0.05 for significant association in initial screening with the chi-square test.
Results. Evaluation of genotype distributions by the chi-square test and subsequent multivariable logistic regression analysis with adjustment for age and sex revealed that seven polymorphisms [−1131T→ C, −3A→G, and 553G→T (Gly185Cys) of APOA5; 1100C→T of APOC3; 85T→C of APOA1; 41A→G (Glu14Gly) of ACAT2; C→G (Ser47Stop) of LPL] were significantly (FDR < 0.05) associated with hypertriglyceridemia in subject panel A. To validate these associations, we examined the same polymorphisms in subject panel B. The six polymorphisms of APOA5, APOC3, APOA1, and LPL, but not that of ACAT2, were again significantly associated with hypertriglyceridemia. Serum triglyceride concentrations differed significantly (P<0.05, ANOVA) among genotypes of each of these six polymorphisms in both subject panels. The three polymorphisms of APOA5 were in linkage disequilibrium.
Conclusions. Polymorphisms of APOA5, APOC3, APOA1, and LPL are determinants of hypertriglyceridemia. Genotyping of these polymorphisms may prove informative for assessment of the genetic risk for hypertriglyceridemia and may contribute to the personalized prevention of this condition.