Insulin resistance after precocious pubarche: relation to PAI-1-675 4G/5G polymorphism, and opposing influences of prenatal and postnatal weight gain

• Published in: Clinical endocrinology (Oxford) 2007-10, Vol.67 (4), p.493-499
• Main Authors: López-Bermejo, Abel, Casano-Sancho, Paula, Petry, Clive J., Jaramillo, Adriana M., Rodríguez-González, Francesc-Xavier, Dunger, David B., De Zegher, Francis, Ibáñez, Lourdes
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Body Mass Index; Case-Control Studies; Chi-Square Distribution; Child; Cross-Sectional Studies; Endocrinopathies; European Continental Ancestry Group; Female; Fundamental and applied biological sciences. Psychology; Genotype; Gynecology. Andrology. Obstetrics; Humans; Infant, Low Birth Weight; Infant, Newborn; Insulin - metabolism; Insulin Resistance - genetics; Insulin Secretion; Insulin-Secreting Cells - metabolism; Linear Models; Medical sciences; Plasminogen Activator Inhibitor 1 - genetics; Polymorphism, Genetic; Puberal and climacteric disorders (male and female); Puberty, Precocious - ethnology; Puberty, Precocious - genetics; Puberty, Precocious - physiopathology; Vertebrates: endocrinology; Weight Gain
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/j.1365-2265.2007.02914.x

Summary Objective   The common promoter –675 4G/5G insertion/deletion polymorphism (indel) in the plasminogen activator inhibitor‐1 (PAI‐1) gene has been associated with quantitative components of the metabolic syndrome. We hypothesized that this polymorphism is associated with precocious pubarche (PP), a population known to be at risk for hyperinsulinaemic hyperandrogenism. Design   A cross‐sectional, hospital‐based study. Patients   A total of 115 control and 182 PP Catalan girls and young women. Measurements   Subjects were genotyped for the –675 4G/5G indel in the PAI‐1 gene. Insulin resistance and insulin secretion were estimated by the homeostasis model assessment. Results   Genotype frequencies for the PAI‐1–675 4G/5G indel (4G4G, 4G5G and 5G5G) were similar in control and PP subjects (24%vs. 27%, 50%vs. 47%, and 26%vs. 26%, respectively; P = 0·85) and these frequencies were in Hardy–Weinberg equilibrium. The 5G allele, however, was associated with insulin resistance in both postmenarcheal control and PP subjects (P