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

Abstract

Objective: To assess whether the K11391GOA polymorphism in the regulatory region of the adiponectin gene (ADIPOQ) is associated with birth size, postnatal growth, adiponectinemia, and cardiometabolic risk in adult life. Design: Case-control study nested within a prospective cohort of 2063 community subjects born in 1978/1979 and followed since birth to date. Methods: ADIPOQ K11391GOA 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). Results: The K11391A variant allele frequency was higher in LGA subjects (PZ0.04). AA genotype was associated with augmented probability of being born LGA (odds ratioZ4.14; 95% confidence interval: 1.16-16.7; PZ0.03). This polymorphism was associated neither with body composition nor with postnatal growth pattern. At the age of 23-25 years, the K11391A variant allele was associated with higher serum adiponectin levels (GG: 10.7G6.2 versus GA: 12.2G6.5 versus AA: 14.2 G6.8 mg/ml; P!0.01). Subjects born LGA presented higher body mass index (BMI; PZ0.01), abdominal circumference (PZ0.04), blood pressure (PZ0.04), and homeostasis assessment model for insulin resistance (PZ0.01) 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. Conclusions: The K11391A ADIPOQ gene variant was associated with increased chance of being born LGA and with higher adiponectin levels in early adult life.

Small and large size for gestational age at birth, infant growth, and childhood overweight

“…Furthermore, among children born LGA, the risk of childhood overweight is modified by infant catch-down growth, with the highest risk of being overweight when not showing catch-down growth. This is in line with the study by Bueno et al among 116 children born LGA, showing that catchdown growth was associated with a lower BMI and abdominal circumference at the age of 23-25 years (29). Longer follow-up in this study population and other populations is needed to assess whether these associations persist and other associations develop in adolescence and adulthood.…”

Association of adiponectin polymorphism with cord blood adiponectin concentrations and intrauterine growth

“…A case-control study in the Brazilian population demonstrated that the rs17300539 A allele in ADIPOQ was significantly associated with an increased chance of large-for-gestational-age birth, but the study did not measure circulating adiponectin levels at birth. 40 Because the rs17300539 A allele is very rare in Japanese (monoallelic in HapMap JPT and HapMap CHB), we did not genotype rs17300539 in our study. 41 We showed that the positive correlation between the rs266729 SNP in ADIPOQ and birth weight s.d.…”

Progression of Cardio-Metabolic Risk Factors in Subjects Born Small and Large for Gestational Age

“…Children born small (SGA) and large (LGA) for gestational age are at greater risk of developing type 2 diabetes and cardiovascular disease as they age [1]–[6]. These groups have been shown to have metabolic alterations in childhood and adolescence, suggesting a phenotype of metabolic dysfunction in early life, finally leading to the emergence of disease in adulthood [2], [6]–[10].…”