Gene–gene interaction between PPARγ2 and ADRβ3 increases obesity risk in children and adolescents

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Abstract
AIMS: Multiple genes are likely to be involved in obesity and these genes may interact with environmental factors to influence obesity risk. Our aim was to explore the synergistic contribution of the two polymorphisms: Pro12Ala of the PPARγ2 gene and Trp64Arg of the ADRβ3 gene to obesity risk in a Spanish children and adolescent population. METHODS: We designed a sex- and age-matched case–control study. Participants were 185 obese and 185 control children (aged 5–18 y) from the Navarra region, recruited through Departments of Pediatrics (Hospital Virgen del Camino, Navarra University Clinic and several Primary Health Centers). The obesity criterion (case definition) was BMI above the 97th percentile according to Spanish BMI reference data for age and gender. Anthropometric parameters were measured by standard protocols. The genotype was assessed by PCR-RFLP after digestion with BstUI for PPARγ2 mutation and BstNI for ADRβ3 variants. Face-to-face interviews were conducted to assess the physical activity. Using a validated physical activity questionnaire, we computed an activity metabolic equivalent index (METs h/week), which represents the physical exercise during the week for each participant. Statistical analysis was performed by conditional logistic regression, taking into account the matching between cases and controls. RESULTS: Carriers of the polymorphism Pro12Ala of the PPARγ2 gene had a significantly higher obesity risk than noncarriers (odds ratio (OR)=2.18, 95% CI=1.09–4.36) when we adjusted for sex, age and physical activity. Moreover, the risk of obesity was higher (OR=2.59, 95% CI=1.17–5.34) when family history of obesity was also taken into account in the model. The OR for obesity linked to both polymorphisms (PPARγ2 and ADRβ3) was 5.30 (95% CI=1.08–25.97) when we adjusted for sex, age and physical activity. After adjustment for family history of obesity, the OR for carriers of both polymorphisms was 19.5 (95% CI=2.43–146.8). CONCLUSIONS: A synergistic effect between polymorphism Pro12Ala of the PPARγ2 gene and Trp64Arg of the ADRβ3 gene for obesity risk was found in a case–control study including children and adolescents.

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