Insulin resistance after precocious pubarche: relation to PAI-1-675 4G/5G polymorphism, and opposing influences of prenatal and postnatal weight gain.
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.
López-Bermejo
Abel
A
Diabetes, Endocrinology and Nutrition Unit, Dr Josep Trueta Hospital, Girona, Spain. uden.alopez@htrueta.scs.es
Casano-Sancho
Paula
P
Petry
Clive J
CJ
Jaramillo
Adriana M
AM
Rodríguez-González
Francesc-Xavier
FX
Dunger
David B
DB
de Zegher
Francis
F
Ibáñez
Lourdes
L
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
D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1