Insulin resistance after precocious pubarche: relation to PAI-1–675 4G/5G polymorphism, and opposing influences of prenatal and postnatal weight gain
Abel López-Bermejo,
Paula Casano-Sancho,
Clive J. Petry,
Adriana M. Jaramillo,
Francesc-Xavier Rodríguez-González,
David B. Dunger,
Francis De Zegher,
Lourdes Ibáñez,
Abel López-Bermejo
Diabetes, Endocrinology and Nutrition Unit, Dr Josep Trueta Hospital, Girona, Spain,
Search for more papers by this authorPaula Casano-Sancho
Endocrinology Unit, Sant Joan de Déu Children's Hospital, Esplugues, Barcelona, Spain,
Search for more papers by this authorClive J. Petry
Department of Paediatrics, University of Cambridge, Cambridge, UK,
Search for more papers by this authorAdriana M. Jaramillo
Endocrinology Unit, Sant Joan de Déu Children's Hospital, Esplugues, Barcelona, Spain,
Search for more papers by this authorFrancesc-Xavier Rodríguez-González
Diabetes, Endocrinology and Nutrition Unit, Dr Josep Trueta Hospital, Girona, Spain,
Search for more papers by this authorDavid B. Dunger
Department of Paediatrics, University of Cambridge, Cambridge, UK,
Search for more papers by this authorFrancis De Zegher
Department of Pediatrics, University of Leuven, Leuven, Belgium
Search for more papers by this authorLourdes Ibáñez
Endocrinology Unit, Sant Joan de Déu Children's Hospital, Esplugues, Barcelona, Spain,
Search for more papers by this authorAbel López-Bermejo,
Paula Casano-Sancho,
Clive J. Petry,
Adriana M. Jaramillo,
Francesc-Xavier Rodríguez-González,
David B. Dunger,
Francis De Zegher,
Lourdes Ibáñez,
Abel López-Bermejo
Diabetes, Endocrinology and Nutrition Unit, Dr Josep Trueta Hospital, Girona, Spain,
Search for more papers by this authorPaula Casano-Sancho
Endocrinology Unit, Sant Joan de Déu Children's Hospital, Esplugues, Barcelona, Spain,
Search for more papers by this authorClive J. Petry
Department of Paediatrics, University of Cambridge, Cambridge, UK,
Search for more papers by this authorAdriana M. Jaramillo
Endocrinology Unit, Sant Joan de Déu Children's Hospital, Esplugues, Barcelona, Spain,
Search for more papers by this authorFrancesc-Xavier Rodríguez-González
Diabetes, Endocrinology and Nutrition Unit, Dr Josep Trueta Hospital, Girona, Spain,
Search for more papers by this authorDavid B. Dunger
Department of Paediatrics, University of Cambridge, Cambridge, UK,
Search for more papers by this authorFrancis De Zegher
Department of Pediatrics, University of Leuven, Leuven, Belgium
Search for more papers by this authorLourdes Ibáñez
Endocrinology Unit, Sant Joan de Déu Children's Hospital, Esplugues, Barcelona, Spain,
Search for more papers by this author Dr Abel López-Bermejo, Diabetes, Endocrinology and Nutrition Unit, Dr Josep Trueta Hospital, Avenue. de Francia, s/n 17007 Girona, Spain. Tel.: +34-972-940200 ext. 2580; Fax: +34-972-940270; E-mail: [email protected]
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 < 0·01 for pooled postmenarcheal subjects, N = 122). The coexistence with the at-risk genotype of both a low birthweight (standard deviation score, SDS < –1·0) and a high body mass index (BMI) at time of the study (SDS > +1·0) resulted in a noteworthy increase (P < 0·001) in insulin resistance.
Conclusion The common promoter –675 4G/5G indel of the PAI-1 gene is not associated with PP but, in Catalan young women, the 5G allele enhances the risk for insulin resistance imposed by the sequence of a low birth weight (LBW) and a high BMI.
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