Original Article
International Journal of Obesity (2006) 30, 1522–1528. doi:10.1038/sj.ijo.0803314; published online 28 March 2006
Polymorphisms in the NPY and AGRP genes and body fatness in Dutch adults
C T M van Rossum1, H Pijl2, R A H Adan3, B Hoebee4 and J C Seidell5
- 1Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
- 2Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
- 3Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
- 4Laboratory of Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
- 5Department for Nutrition and Health, Free University of Amsterdam, Amsterdam, The Netherlands
Correspondence: Dr CTM van Rossum, Centre for Nutrition and Health, National Institute for Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, The Netherlands. E-mail: caroline.van.rossum@rivm.nl
Received 25 May 2005; Revised 24 January 2006; Accepted 16 February 2006; Published online 28 March 2006.
Abstract
Objective:
To investigate the association between DNA polymorphisms in the NPY and AGRP genes and body fatness.
Design and methods:
The association between the AGRP Ala67Thr or the NPY Leu7Pro polymorphisms and indicators of body fatness (baseline leptin levels, body mass index (BMI) values and prevalence of overweight) are investigated in 582 participants of two large cohorts in The Netherlands (total 18 500 adult men and women), aged 20–40 years whose weight remained relatively constant or whose weight increased substantially (range 5.5–47 kg) during a mean follow-up of 7 years.
Results:
No consistent associations were found for the indicators of body fatness for men and women. Among women, BMI values, leptin levels and prevalence of overweight were not statistically different for carriers of the mutant alleles compared to that of the non-carriers. Among men, carriers of the Thr67-allele of the AGRP gene had similar leptin levels, but higher BMI values compared to those with the genotyping Ala67/Ala67: mean adjusted BMI 25.6 kg/m2 (95% CI 24.3–27.0) vs 23.9 kg/m2 (23.6–24.3). Also, the risk of being overweight at baseline tended to be higher for male carriers of the Thr67-allele of the AGRP gene (OR 2.52; 95% CI 0.86–7.4). Furthermore, male carriers of the Pro7-allele of the NPY gene had on average higher leptin levels and BMI values vs non-carriers of this allele: 4.7 
g/l (95% CI 3.7–6.0) and 25.7 kg/m2 (95% CI 24.4–27.0) vs 3.1 g/l (95% CI 2.9–3.4) and 23.9 kg/m2 (95% CI 23.5–24.3), respectively. These male carriers had also a higher risk on being overweight at baseline (OR 3.3 (95% CI 1.2–8.9)) compared to non-carriers of the Pro7-allele.
Conclusion:
The consistent findings among men suggest that the NPY Leu7Pro polymorphism (or another linked marker) might be involved in the development of obesity at younger ages. The findings for the AGRP Ala67Thr were less consistent and need further investigation. Among women, these polymorphisms do not play an important role.
Keywords:
epidemiology, genetics, candidate genes, agouti-related protein, neuropeptide Y
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