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The Association between the FTO Gene and Fat Mass in Humans Develops by the Postnatal Age of Two Weeks

Diabetes, Endocrinology and Nutrition Unit (A.L.-B.), Dr. Josep Trueta Hospital, 17007 Girona, Spain; Department of Paediatrics (C.J.P., D.B.D.), University of Cambridge, Cambridge CB2 2QQ, United Kingdom; Endocrinology Unit (M.D., G.S., L.I.), Sant Joan de Déu Children’s Hospital, University of Barcelona, 08950 Esplugues, Barcelona, Spain; and Department of Woman and Child (F.d.Z.), University of Leuven, 3000 Leuven, Belgium

Address all correspondence and requests for reprints to: Lourdes Ibáñez, M.D., Ph.D., Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain. E-mail: libanez{at}hsjdbcn.org.

Objective: Little is known about the genetic determinants of fat mass around birth. We hypothesized that the common rs9939609 single-nucleotide polymorphism (SNP) in FTO is associated with fat mass and metabolic parameters in neonates.

Design: We conducted a cross-sectional, hospital-based study.

Patients: Patients included 234 full-term, healthy newborns [122 girls and 112 boys; gestational age (mean, range), 39.0 (37.0–42.0) wk; birth weight, 3.2 (1.9–4.2) kg].

Methods: Cord-blood insulin, IGF-I, IGF-binding protein-1, adiponectin, and visfatin were measured by specific immunoassays. Body composition was assessed by dual-energy x-ray absorptiometry at about 13 d (range, 9–20 d). Genotyping of rs9939609 was achieved by restriction fragment length polymorphism analysis.

Results: The rs9939609 SNP in FTO was not associated with birth weight; however, it was associated with serum visfatin (P < 0.001), with weight and ponderal index at age 2 wk (P < 0.05), and with total, truncal, and abdominal fat (P < 0.05 to P = 0.01), so that AA homozygotes had 37% higher plasma visfatin concentration and 17, 20, and 17% higher total, truncal, and abdominal fat mass, respectively, than T-carrier neonates.

Conclusion: Our findings support a role of the common rs9939609 SNP in FTO gene in the early stages of fat accretion in humans and disclose novel associations between this SNP and both serum visfatin and abdominal fat mass in neonates.