Allelic variations of the D2 dopamine receptor gene in children with idiopathic short stature.

The D2 dopamine receptor (DRD2) plays a major role in growth hormone (GH) secretion. Recent reports indicate that Taq I A DRD2 gene alleles (A1 and A2) are related to the function of DRD2. Idiopathic short stature (ISS) is defined as short stature without accompanying malnutrition, chronic disease, and endocrinological disorders. However, some reports suggest that ISS is associated with a mild disturbance of GH secretion. In this study, we examined the notion that allelic variants of the DRD2 are associated with ISS. We studied 55 children with ISS aged 8.4 (SD 2.9) years; (group I) and 104 age-matched children of normal stature (group II). Informed consent was obtained from each child's parent or guardian. Genomic DNAs were extracted from peripheral mononuclear cells and amplified by polymerase chain reaction (PCR). The PCR products were digested by Taq1 and resolved by electrophoresis. The frequency of the A1 allel was significantly higher in group I (0.42) than in group II (0.26). The insulin-like growth factor (IGF)-I ratio (the ratio of the individual level to the normal mean value according to age at our laboratory center) was significantly lower in group I than in group II. When group I was subdivided into group A (with the A1 allele) and group B (with only the A2 allele), group A had a significantly lower peak GH response to the l-dopa test, lower levels of IGF-I, and retarded bone maturation. These findings indicate that polymorphism of the DRD2 gene may be one genetic factor that affects body height in childhood, acting through the hypothalamus (GH-releasing hormone)--pituitary (GH)--IGF-I axis.