No association between body mass index and β₃-adrenergic receptor variant (W64R) in children with premature pubarche and adolescent girls with hyperandrogenism

Abstract

Objective: To determine if the Trp⁶⁴Arg (W64R) variant of the β₃-adrenergic receptor (ADRB3) could be used as a genetic marker to define risk for polycystic ovary syndrom (PCOS) and/or obesity in children and adolescents.

Design: Association study.

Setting: Academic research environment.

Patient(s): Children referred for evaluation of premature pubic hair (n = 63), adolescent girls referred for evaluation of hirsutism and/or oligomenorrhea (n = 33), and healthy adult controls (n = 67).

Intervention(s): None.

Main Outcome Measure(s): Relationship of body mass index (BMI) to presence or absence of W64R variant and frequency of W64R variant in our patient population.

Result(s): Body mass index (kg/m²) was determined for 63 children (55 girls and 8 boys) and 33 adolescent girls. Presence or absence of the W64R variant was assayed by polymerase chain reaction (PCR) amplification followed by allele-specific restriction fragment digest. Twelve subjects and 11 healthy controls were found to be heterozygous for the W64R variant. One subject was found to be homozygous for the W64R variant. Allele frequency for the W64R variant was comparable between patients and controls. Among the patients, mean BMI values were not different between carriers and noncarriers.

Conclusion(s): Although other studies suggest that the W64R variant is associated with the development of obesity and insulin resistance, we cannot demonstrate that it has a major effect on BMI in children with premature pubarche or in adolescent girls with hyperandrogenism. Serial observations are necessary to determine if this variant predicts the development of obesity and/or PCOS in adulthood.