Adiponectin: serum levels, promoter polymorphism, and associations with birth size and cardiometabolic outcome in young adults born large for gestational age

Abstract

ObjectiveTo assess whether the −11391G>A polymorphism in the regulatory region of the adiponectin gene (ADIPOQ) is associated with birth size, postnatal growth, adiponectinemia, and cardiometabolic risk in adult life.DesignCase–control study nested within a prospective cohort of 2063 community subjects born in 1978/1979 and followed since birth to date.MethodsADIPOQ −11391G>A genotype–phenotype associations were evaluated in 116 subjects born large for gestational age (LGA) and 392 gender-matched controls at birth (birth size), at 8–10 years (catch-down growth), and at 23–25 years of age (cardiometabolic profile).ResultsThe −11391A variant allele frequency was higher in LGA subjects (P=0.04). AA genotype was associated with augmented probability of being born LGA (odds ratio=4.14; 95% confidence interval: 1.16–16.7; P=0.03). This polymorphism was associated neither with body composition nor with postnatal growth pattern. At the age of 23–25 years, the −11391A variant allele was associated with higher serum adiponectin levels (GG: 10.7±6.2 versus GA: 12.2±6.5 versus AA: 14.2±6.8 μg/ml; P<0.01). Subjects born LGA presented higher body mass index (BMI; P=0.01), abdominal circumference (P=0.04), blood pressure (P=0.04), and homeostasis assessment model for insulin resistance (P=0.01) than adequate for gestational age. Symmetry at birth did not influence these variables. The occurrence of catch-down of weight was associated with lower BMI and abdominal circumference (P<0.001) at 23–25 years.ConclusionsThe −11391A ADIPOQ gene variant was associated with increased chance of being born LGA and with higher adiponectin levels in early adult life.