Title: Insulin resistance after precocious pubarche: relation to PAI-1-675 4G/5G polymorphism, and opposing influences of prenatal and postnatal weight gain
Authors: Lopez-Bermejo, Abel ×
Casano-Sancho, Paula
Petry, Clive J
Jaramillo, Adriana M
Rodriguez-Gonzalez, Francesc-Xavier
Dunger, David B
de Zegher, Francis
Ibanez, Lourdes #
Issue Date: 2007
Series Title: Clinical endocrinology vol:67 issue:4 pages:493-499
Conference: date:Dr Josep Trueta Hosp, Endocrinol & Nutr Unit, E-17007 Girona, Spain; Sant Joan Deu Childrens Hosp, Endocrinol Unit, Barcelona, Spain; Univ Cambridge, Dept Paediat, Cambridge, England; Univ Leuven, Dept Pediat, Louvain, Belgium
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.
ISSN: 0300-0664
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Section Newborn (-)
× corresponding author
# (joint) last author

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