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- Title
Insulin resistance after precocious pubarche: relation to PAI-1–675 4G/5G polymorphism, and opposing influences of prenatal and postnatal weight gain.
- 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
- Abstract
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.
- Subjects
INSULIN resistance; GENETIC polymorphisms; FIBRINOLYTIC agents; POLYCYSTIC ovary syndrome; PHYSIOLOGICAL control systems; ANALYSIS of variance
- Publication
Clinical Endocrinology, 2007, Vol 67, Issue 4, p493
- ISSN
0300-0664
- Publication type
Article
- DOI
10.1111/j.1365-2265.2007.02914.x