The Trp64Arg amino acid polymorphism of the beta(3)-adrenergic receptor gene does not contribute to the genetic susceptibility of diabetic microvascular complications in Caucasian type 1 diabetic patients

Objective. The beta(3)-adrenergic receptor is involved in regulation of mic rovascular blood flow. A missense mutation (Trp64Arg) in the beta(3)-adrene rgic receptor gene has been suggested as a risk factor for proliferative re tinopathy in Japanese type 2 diabetic patients. The aim of the present stud y was to evaluate the contribution of this polymorphism to the development of microangiopathic complications in Caucasian type 1 diabetic patients. Subjects and methods. We studied the relationship between the Trp64Arg poly morphism in type 1 diabetic patients with nephropathy (204 men/132 women, a ge 42.8+/-11.0 years, diabetes duration 28+/-9 years) and in type 1 diabeti c patients with persistent normoalbuminuria (118 men/73 women, age 42.6+/-1 0.2 years, diabetes duration 27+/-8 years). Proliferative retinopathy was p resent in 254 patients (48%), while 66 patients (13%) had no diabetic retin opathy. Results. There were no differences in Trp64Arg genotype distribution betwee n type 1 diabetic patients with diabetic nephropathy and type 1 diabetic pa tients with normoalbuminuria: 295 (88%)/38 (11%)/3 (1%) vs 161 (84%)/30 (16 %)/- had Trp/Trp, Trp/Arg or Arg/Arg genotype respectively. Odds ratio (95% CI) of nephropathy in carriers of the mutation was 0.75 (0.45-1.25). No as sociations between the Trp64Arg polymorphism and simplex or proliferative r etinopathy were revealed either. The frequency of the Arg-allele was 0.069 in patients with proliferative retinopathy, 0.066 in patients with simplex retinopathy and 0.090 in patients with no signs of diabetic retinopathy, NS . Conclusions. The Trp64Arg polymorphism of the beta(3)-adrenergic receptor g ene does not contribute to the genetic susceptibility to diabetic nephropat hy in Caucasian type I diabetic patients. Nor does our study support previo us findings of an association between this variant and proliferative retino pathy.