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Sex-specific effect of the Val1483Ile polymorphism in the fatty acid synthase gene (FAS) on body mass index and lipid profile in Caucasian children

International Journal of Obesity volume 31, pages 353–358 (2007)Cite this article

Abstract

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.

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Acknowledgements

We thank all those who participated in the studies. We appreciate the help of the nurses and physicians who performed the clinical examinations and data collection. The help of Roy Tauscher for DNA extraction and consenting is highly appreciated. This work was supported by grants from the Deutsche Forschungsgemeinschaft (KFO-152 to AK and MS) from the Interdisciplinary Center of Clinical Research at the University of Leipzig to AK (B21) and to MS (Z14), from the European Community ‘PIONEER’ (to WK), and from the German Diabetes Association to AK and to PK. The Leipzig schoolchildren project was supported by unrestricted grants from Pfizer Pharma GmbH and Novo Nordisk GmbH to WK. The studies in Pima Indians were supported via the NIDDK Intramural Research Program.

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Authors and Affiliations

  1. University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany

    A Körner & W Kiess

  2. Phoenix Epidemiology and Clinical Research Branch, NIDDK, NIH, Phoenix, AZ, USA

    L Ma, P W Franks & L J Baier

  3. Medicine Department of Public Health & Clinical Medicine, Umeå University Hospital, Umeå, Sweden

    P W Franks

  4. Medical Department III, University of Leipzig, Leipzig, Germany

    M Stumvoll & P Kovacs

Authors
  1. A Körner
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  2. L Ma
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  3. P W Franks
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  4. W Kiess
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  5. L J Baier
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  6. M Stumvoll
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  7. P Kovacs
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Correspondence to P Kovacs.

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Körner, A., Ma, L., Franks, P. et al. Sex-specific effect of the Val1483Ile polymorphism in the fatty acid synthase gene (FAS) on body mass index and lipid profile in Caucasian children. Int J Obes 31, 353–358 (2007). https://doi.org/10.1038/sj.ijo.0803428

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