Objective: A Val1483Ile polymorphism in the human fatty acid sythase gene (FAS) has recently been shown to be associated with lower percentage of body fat and substrate oxidation rates in Pima Indians, but its role in other populations has not been described. Here, we investigate the effect of this variant on obesity in Caucasian children and adolescents.
Subjects and methods: In total, 738 Caucasian children and adolescents aged 6-17 years of the Leipzig Schoolchildren cohort, which constitutes an unselected representative German population and 205 obese children (body mass index (BMI) 2.71+/-0.04 SDS) were genotyped for genotype-phenotype associations.
Results: The frequency of the Ile-allele was lower in German Caucasians compared with Pima Indians (0.03 compared to 0.10). Using generalized linear regression models, there was no effect of the polymorphism on BMI in the whole normal population. However, we identified a significant interaction effect between sex and genotype (P=0.004). Subsequent sex stratified analyses revealed a lower BMI SDS in boys with Ile/Val genotype compared to Val/Val (-0.36+/-0.29 vs 0.09+/-0.05, P<0.05), while an opposite effect was observed in girls (0.48+/-0.19 vs 0.09+/-0.05, P<0.05). In genotype-phenotype associations in obese children, the polymorphism did not affect parameters of insulin, glucose, or lipid metabolism in the whole population. Again, however, obese boys with Ile/Val genotype had significantly higher high-density lipoprotein (HDL) cholesterol levels (1.46+/-0.07 vs 1.23+/-0.03 mmol/l, P<0.05).
Conclusion: In conclusion, our findings suggest a sex-specific protective effect of the Val1483Ile polymorphism in FAS for obesity in Caucasian boys. In addition, the polymorphism may be associated with a beneficial lipid profile in obese boys.