Trp(64)Arg polymorphism of the beta(3)-adrenergic receptor gene in pregnancy: Association with mild gestational diabetes mellitus

A missense mutation of the beta(3)-adrenergic receptor gene (Trp(64)Arg) ha s been associated with obesity and increased capacity to gain weight in non pregnant populations. Furthermore, the mutation is a potential modifying fa ctor in the etiology of impaired glucose tolerance and type 2 diabetes. We studied the relation of the beta(3)-adrenergic receptor genotype to glucose tolerance during pregnancy, a state of physiological insulin resistance. I n 179 pregnant women (mean age, 28.5 +/- 0.4 yr), a 2-h oral glucose tolera nce test was performed between gestational weeks 20 and 31. The beta(3)-adr energic receptor genotype was assessed using restriction fragment length po lymorphism. The frequency of the Arg(64) allele was 9.15%. In women with mild gestation al diabetes (n = 70), as defined by 60 min postload glucose values, the Trp (64)Arg genotype was more frequent than in women with normal glucose tolera nce (n = 109; 26% us. 11%; P = 0.01). Furthermore, the Trp64Arg polymorphis m was associated with increased weight gain during pregnancy (baseline to g estational weeks 20-31) and increased postload glucose, insulin, and C pept ide values during the oral glucose tolerance test. The results of the present study extend current knowledge about the associa tion of the Trp(64)Arg beta(3)-adrenergic receptor polymorphism with glucos e tolerance to a pregnant population. The association with mild gestational diabetes suggests that the impact of the polymorphism may be clinically im portant during pregnancy, a state of physiological insulin resistance.