The PPAR-gamma Pro12Ala polymorphism associates with weight gain during GH-treatment in short children born small for gestational age.

Context: Short children born small for gestational age (SGA) have a lean phenotype with lower insulin sensitivity and higher blood pressure. GH treatment results in weight gain, and a decrease in blood pressure and insulin sensitivity. However, not all children respond in the same way. The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR-gamma) gene is inversely associated with body mass index (BMI), changes in BMI and the risk to develop type 2 diabetes mellitus.

Objective: To analyze the contribution of the PPAR-gamma Pro12Ala polymorphism to GH induced changes in determinants of metabolic and cardiovascular disease in short SGA children.

Methods: PPAR-gamma was genotyped in 238 Caucasian short SGA children (mean age 7.5 years). Height, weight, blood pressure, and serum lipids were measured before start and during 4 years of GH treatment. In addition, glucose homeostasis by homeostasis model assessment insulin resistance ratio (HOMA-IR) (n=148) and by frequently sampled i.v. glucose tolerance test (n=51), and body composition by dual energy X-ray absorptiometry (n=79) were measured.

Results: At baseline, the Ala12 allele was not associated with any determinant of metabolic and cardiovascular disease. After 4 years of GH treatment, the increase in weight for height SDS and BMI SDS was significantly greater in carriers of an Ala12 allele than in noncarriers. The change in all other parameters was not associated with Pro12Ala genotype.

Conclusion: The Ala12 variant of the PPAR-gamma gene is associated with higher weight gain during GH treatment but not with changes in determinants of metabolic and cardiovascular diseases in Caucasian subjects born SGA.