Effects of intestinal fatty acid-binding protein gene Ala54Thr polymorphism and β₃-adrenergic receptor gene Trp64Arg polymorphism on insulin resistance and fasting plasma glucose in young to older Japanese men

The present study was performed to investigate the effects of the intestinal fatty acid-binding protein (FABP2) gene Ala54Thr polymorphism and the β₃-adrenergic receptor (β3AR) gene Trp64Arg polymorphism on body mass index (BMI), blood pressure, heart rate, glucose and lipid profiles, and serum leptin level in 196 young men aged 21 to 39 years, 186 older normoglycemic men (fasting plasma glucose [FPG] < 110 mg/dL) aged 40 to 65 years, and 122 older hyperglycemic men, including 77 type 2 diabetic patients. Genomic DNA was extracted from the peripheral blood, and these polymorphisms were assessed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. In the older groups, the β3AR Arg64-allele frequency tended to be lower and the FABP2 Thr/Thr54 genotype frequency tended to be higher in hyperglycemic patients, although these differences did not reach statistical significance. Also, there were no significant differences in the genotype or allele frequency of either variant between the 27 hyperlipidemic and 204 normolipidemic subjects. In the younger group, there were no significant differences in any of the parameters measured between the genotypes of β3AR or FABP2. In the older normoglycemic subjects, heart rate was significantly lower (P =.037) in β3AR Arg64-positive subjects, and FPG was significantly higher in subjects with the FABP2 Thr/Thr genotype than the other genotypes (99.8 ± 5.6 v 96.5 ± 5.6 mg/dL, P =.010). In the older hyperglycemic group, the β3AR Arg64-positive group had significantly lower high-density lipoprotein (HDL) cholesterol and free fatty acid (FFA) levels (P =.024 and P =.043, respectively). There were no synergistic effects of these 2 variants on any measured parameter, but only the FABP2 Thr/Thr genotype was related to a higher FPG in the older normoglycemic men. In conclusion, no major difference was associated with the β3AR Trp64Arg or FABP2 Ala54Thr polymorphism in terms of type 2 diabetes or hyperlipidemia in young to older Japanese men. However, a slight but significant increase in FPG was observed in older Japanese men with the FABP2 Thr/Thr genotype.