Abstract

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. 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. 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. 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.

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