Effects of intestinal fatty acid-binding protein gene Ala54Thr polymorphism and beta(3)-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 intestina l fatty acid-binding protein (FABP2) gene Ala54Thr polymorphism and the bet a (3)-adrenergic receptor (beta 3AR) gene Trp64Arg polymorphism on body mas s 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 normogly cemic men (fasting plasma glucose [FPG] < 110 mg/dL) aged 40 to 65 years, a nd 122 older hyperglycemic men, including 77 type 2 diabetic patients. Geno mic DNA was extracted from the peripheral blood, and these polymorphisms we re assessed by the polymerase chain reaction (PCR)-restriction fragment len gth polymorphism (RFLP) method. In the older groups, the beta 3AR Arg64-all ele 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 dif ferences in the genotype or allele frequency of either variant between the 27 hyperlipidemic and 204 normo-lipidemic subjects. In the younger group,th ere were no significant differences in any of the parameters measured betwe en the genotypes of beta 3AR or FABP2. In the older normoglycemic subjects, heart rate was significantly lower (P = .037) in beta 3AR Arg64-positive s ubjects, and FPG was significantly higher in subjects with the FABP2 Thr/Th r genotype than the other genotypes (99.8 +/- 5.6 v 96.5 +/- 5.6 mg/dL, P = .010). In the older hyperglycemic group, the beta 3AR Arg64-positive group had significantly lower high-density lipoprotein (HDL) cholesterol and fre e 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 no rmoglycemic men. In conclusion, no major difference was associated with the beta 3AR Trp64Arg or FABP2 Ala54Thr polymorphism in terms of type 2 diabet es or hyperlipidemia in young to older Japanese men. However, a slight but significant increase in FPG was observed in older Japanese men with the FAB P2 Thr/Thr genotype. Copyright (C) 2001 by W.B. Saunders Company.