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Trp⁶⁴Arg Polymorphism of the ß₃-Adrenergic Receptor Gene in Pregnancy: Association with Mild Gestational Diabetes Mellitus

Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center (A.F., S.H.), San Antonio, Texas 78284; and the Department of Medicine 1 (A.F., N.S., G.S.) and the Institute of Clinical Chemistry (W.K., P.H.), Rudolfstiftung Hospital, Vienna, Austria

Address all correspondence and requests for reprints to: Andreas Festa, M.D., Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7873. E-mail: festa{at}uthscsa.edu

A missense mutation of the ß₃-adrenergic receptor gene (Trp⁶⁴Arg) has been associated with obesity and increased capacity to gain weight in nonpregnant populations. Furthermore, the mutation is a potential modifying factor in the etiology of impaired glucose tolerance and type 2 diabetes. We studied the relation of the ß₃-adrenergic receptor genotype to glucose tolerance during pregnancy, a state of physiological insulin resistance. In 179 pregnant women (mean age, 28.5 ± 0.4 yr), a 2-h oral glucose tolerance test was performed between gestational weeks 20 and 31. The ß₃-adrenergic receptor genotype was assessed using restriction fragment length polymorphism.

The frequency of the Arg⁶⁴ allele was 9.15%. In women with mild gestational diabetes (n = 70), as defined by 60 min postload glucose values, the Trp⁶⁴Arg genotype was more frequent than in women with normal glucose tolerance (n = 109; 26% vs. 11%; P = 0.01). Furthermore, the Trp⁶⁴Arg polymorphism was associated with increased weight gain during pregnancy (baseline to gestational weeks 20–31) and increased postload glucose, insulin, and C peptide values during the oral glucose tolerance test.

The results of the present study extend current knowledge about the association of the Trp⁶⁴Arg ß₃-adrenergic receptor polymorphism with glucose tolerance to a pregnant population. The association with mild gestational diabetes suggests that the impact of the polymorphism may be clinically important during pregnancy, a state of physiological insulin resistance.

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