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Effect of genetic variation in the leptin gene promoter and the leptin receptor gene on obesity risk in a population-based case-control study in Spain

  • Genetic Epidemiology
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Abstract

There are no good genetic markers for incorporating the study of genetic susceptibility to obesity in epidemiological studies. In animal models, the leptin (LEP) and the leptin receptor (LEPR) genes have been shown to be very important in obesity because leptin functions as a negative feedback signal in regulating body-weight through reducing food intake and stimulating energy expenditure. In humans, several polymorphisms in these genes have been described. However, their association with obesity is still very controversial because there are no good case-control studies designed to specifically test this association. Our objective has been to conduct a population-based case-control study to estimate the risk of obesity arising from the −2548G > A and Q223R polymorphisms in the LEP and LEPR genes, respectively. 303 obese cases (101 men and 202 women) and 606 controls (202 men and 404 women) were selected from a Spanish Mediterranean population. Genetic, clinical and life-style characteristics were analyzed. No association was found between the −2548G > A polymorphism and obesity. However, the Q223R variant was significantly associated with obesity in a recessive model, the RR genotype being more prevalent in controls than in obese subjects. The inverse association between the Q223R polymorphism and obesity (OR = 0.62; 95% CI: 0.39–0.99) remained significant even after additional adjustment for education, tobacco smoking, alcohol, physical activity, origin of the obese patient, and the −2548G > A polymorphism in the LEP gene (OR = 0.54; 95% CI: 0.32–0.89). In conclusion, the −2548G > A polymorphism is not a relevant obesity marker in this Mediterranean population, although Q223R does seen to be so.

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Acknowledgements

This work has been supported by grant GV2004B/310 from the Consellería de Empresa, Universidad y Ciencia, Generalitat Valenciana, and grant G03/160 from the Instituto de Salud Carlos III, Spain.

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Authors and Affiliations

  1. Genetic and Molecular Epidemiology Unit. Department of Preventive Medicine and Public Health. School of Medicine, University of Valencia, Avda. Blasco Ibañez, 15, 46010, Valencia, Spain

    Olga Portolés, José Vicente Sorlí, Francesc Francés, Jose I. González, Carmen Sáiz & Dolores Corella

  2. Department of Computer Languages and Systems, Jaume I University, Castellón, Spain

    Olga Portolés & Oscar Coltell

  3. Centro de Salud de Xirivella, Conselleria de Sanidad, Valencia, Spain

    José Vicente Sorlí

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  1. Olga Portolés
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  2. José Vicente Sorlí
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Correspondence to Dolores Corella.

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Portolés, O., Sorlí, J.V., Francés, F. et al. Effect of genetic variation in the leptin gene promoter and the leptin receptor gene on obesity risk in a population-based case-control study in Spain. Eur J Epidemiol 21, 605–612 (2006). https://doi.org/10.1007/s10654-006-9045-6

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