Effects of the Trp64Arg polymorphism in the beta3-adrenergic receptor gene on insulin sensitivity in small for gestational age neonates

J Clin Endocrinol Metab. 2004 Oct;89(10):4981-5. doi: 10.1210/jc.2003-032027.


To evaluate whether the Trp64Arg polymorphism in the beta3-adrenergic receptor (AR) gene is associated with decreased birth weight and might account for some of the association between birth weight and impaired insulin sensitivity, the beta3-AR genotype was assessed in 296 neonates of singleton pregnancies, including 76 neonates classified as small for gestational age (SGA) and 220 neonate classified as appropriate for gestational age (AGA). Fasting glucose and insulin levels were measured on d 3 after birth. The insulin levels and insulin-to-glucose ratio were significantly higher in the SGA group than in the AGA group. Frequency of the Trp64Arg allele was similar in the AGA and SGA groups (0.15 and 0.17, respectively). Moreover, when we adjusted for sex and gestational age, there was no significant difference in birth weight, fasting glucose, insulin levels, or insulin-to-glucose ratio between those with and without the mutation. However, in the SGA group, carriers of the Trp64Arg allele had significantly higher fasting insulin levels and insulin-to-glucose ratios than noncarriers (17.54 +/- 2.11 vs. 13.18 +/- 1.47 microIU/ml, P < 0.05; and 4.89 +/- 0.60 vs. 3.14 +/- 0.42, P < 0.05, respectively), whereas no association was detected for this polymorphism in the AGA group.SGA is an important factor that predisposes to insulin resistance, and the Trp64Arg beta3-AR gene polymorphism may contribute to insulin resistance associated with reduced fetal growth.

MeSH terms

  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age*
  • Insulin / blood
  • Insulin Resistance / genetics*
  • Male
  • Polymorphism, Genetic*
  • Receptors, Adrenergic, beta-3 / genetics*
  • Risk Factors


  • Insulin
  • Receptors, Adrenergic, beta-3