title: Insulin resistance after precocious pubarche: relation to PAI-1-675 4G/5G polymorphism, and opposing influences of prenatal and postnatal weight gain.
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.
  
  
  METHODS
  A cross-sectional, hospital-based study.
  
  
  METHODS
  A total of 115 control and 182 PP Catalan girls and young women.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Diabetes, Endocrinology and Nutrition Unit, Dr Josep Trueta Hospital, Girona, Spain. uden.alopez@htrueta.scs.es
authors.forename: Abel
authors.initials: A
authors.lastname: López-Bermejo
authors.forename: Paula
authors.initials: P
authors.lastname: Casano-Sancho
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Petry
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Jaramillo
authors.forename: Francesc-Xavier
authors.initials: FX
authors.lastname: Rodríguez-González
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.forename: Francis
authors.initials: F
authors.lastname: de Zegher
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D016014:Linear Models; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011629:Puberty, Precocious / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D015430:Weight Gain; D044465:White People
chemical_list: D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1