Abstract 3939: Prediction of Genetic Risk for Metabolic Syndrome
Objectives: Metabolic syndrome is a highly prevalent disorder, affecting nearly one in four adults (a total of 47 million individuals) in the United States. Several environmental factors, including smoking, a high-calorie diet, and physical inactivity, influence the development of metabolic syndrome, with insulin resistance being considered the underlying metabolic defect. Genetic factors have been shown to also contribute to individual susceptibility to metabolic syndrome. The aim of the present study was to identify gene polymorphisms that confer susceptibility to metabolic syndrome in order to allow reliable assessment of genetic risk for this condition.
Methods and Results: The study population comprised 1788 unrelated Japanese individuals (1033 men, 755 women), including 1017 subjects with metabolic syndrome (634 men, 383 women) and 771 controls (399 men, 372 women). The genotypes for 158 polymorphisms of 133 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of smoking revealed that the -1131T→C polymorphism of the apolipoprotein A-V gene (APOA5) was significantly (P < 0.0009) associated with the prevalence of metabolic syndrome, with the C allele representing a risk factor for this condition. A stepwise forward selection procedure demonstrated that APOA5 genotype (CC + TC versus TT) significantly affected the prevalence of metabolic syndrome (dominant model; P = 0.000003, R2 = 0.0091). The C allele of this polymorphism was associated with an increased serum concentration of triglycerides and a decreased concentration of HDL-cholesterol.
Conclusions: Genotype for APOA5 may prove reliable for assessment of genetic risk for metabolic syndrome.