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OBJECTIVE- We examined whether the PPARy2 Alal2 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. PPARγ^sup 2^ 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% (Prol2Pro), 20.7% (Prol2Ala), and 1.7% (Alal2Ala). Growth rates in weight from second trimester of pregnancy to 18 months were higher for Prol2Ala and Alal2Ala than for Prol2Pro 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, PPARγ^sup 2^ Pro 12Ala was not associated with growth rate. When breast-feeding duration was <2 months or 2-4 months, growth rate was higher in Alal2Ala than Prol2Pro carriers (differences 9.80 g/week [3.97-15.63] and 6.32 g/week (-1.04 to 13.68], respectively).
CONCLUSIONS- The PPARγ^sup 2^ Alal2 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. Diabetes 58:992-999, 2009
Previous studies have shown that common polymorphisms of peroxisome proliferator-activated receptor γ^sup 2^ (PPARγ^sup 2^) are associated with adipocyte differentiation, lipid metabolism, and insulin sensitivity (1). Recent genome-wide association (GWA) studies found consistent and robust associations of the PPARγ2 Prol2Ala polymorphism (rsl801282) with type 2 diabetes (2,3). Furthermore, several studies have reported increased BMI in PPARγ2 Alal2 carriers (4-6). In a meta-analysis, Masud et al. (4) found that in adults with a BMI >27 kg/m^sup 2^ carriers of the PPARγ2 Alal2 allele had an increased BMI. Also, in subjects with normal BMI, they found a significant increase in BMI in Ala 12A1a carriers versus Prol2Pro carriers. However, a recent GWA study on BMI in more than 80,000 subjects did not identify the PPARγ2 Alal2 allele as a variant...