Breast-Feeding Modifies the Association of PPARγ2 Polymorphism Pro12Ala With Growth in Early Life: The Generation R Study

OBJECTIVE: We examined whether the PPARγ2 Ala12 allele influences growth in early life and whether this association is modified by breast-feeding. RESEARCH DESIGN AND METHODS: This study was embedded in the Generation R Study, a prospective cohort study from early fetal life onward. PPARγ2 was genotyped in DNA obtained from cord blood samples in 3,432 children. Information about breast-feeding was available from questionnaires. Weight, head circumference, and femur length were repeatedly measured in second and third trimesters of pregnancy, at birth, and at the ages of 1.5, 6, 11, 14, and 18 months. RESULTS: Genotype frequency distribution was 77.6% (Pro12Pro), 20.7% (Pro12Ala), and 1.7% (Ala12Ala). Growth rates in weight from second trimester of pregnancy to 18 months were higher for Pro12Ala and Ala12Ala than for Pro12Pro carriers (differences 1.11 g/week [95% CI 0.47–1.74] and 2.65 g/week [0.45–4.87], respectively). We found an interaction between genotype and breast-feeding duration (P value for interaction <0.0001). In infants who were breast-fed for ≥4 months, PPARγ2 Pro12Ala was not associated with growth rate. When breast-feeding duration was <2 months or 2–4 months, growth rate was higher in Ala12Ala than Pro12Pro carriers (differences 9.80 g/week [3.97–15.63] and 6.32 g/week [−1.04 to 13.68], respectively). CONCLUSIONS: The PPARγ2 Ala12 allele is associated with an increased growth rate in early life. This effect may be influenced by breast-feeding duration. Further studies should replicate these findings, identify the underlying mechanisms, and assess whether these effects persist into later life.