The Trp64Arg amino acid polymorphism of the beta3-adrenergic receptor gene does not contribute to the genetic susceptibility of diabetic microvascular complications in Caucasian type 1 diabetic patients.

Objective: The beta3-adrenergic receptor is involved in regulation of microvascular blood flow. A missense mutation (Trp64Arg) in the beta3-adrenergic receptor gene has been suggested as a risk factor for proliferative retinopathy in Japanese type 2 diabetic patients. The aim of the present study 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 polymorphism in type 1 diabetic patients with nephropathy (204 men/132 women, age 42.8 +/- 11.0 years, diabetes duration 28 +/- 9 years) and in type 1 diabetic patients with persistent normoalbuminuria (118 men/73 women, age 42.6 +/- 10.2 years, diabetes duration 27 +/- 8 years). Proliferative retinopathy was present in 254 patients (48%), while 66 patients (13%) had no diabetic retinopathy.

Results: There were no differences in Trp64Arg genotype distribution between type 1 diabetic patients with diabetic nephropathy and type 1 diabetic patients 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 associations between the Trp64Arg polymorphism and simplex or proliferative retinopathy 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 beta3-adrenergic receptor gene does not contribute to the genetic susceptibility to diabetic nephropathy in Caucasian type 1 diabetic patients. Nor does our study support previous findings of an association between this variant and proliferative retinopathy.