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Association between liver X receptor α gene polymorphisms and risk of metabolic syndrome in French populations

International Journal of Obesity volume 32, pages 421–428 (2008)Cite this article

Abstract

Context:

The metabolic syndrome is a complex and multifactorial disorder often associated with type 2 diabetes mellitus and cardiovascular diseases. The liver X receptor α (NR1H3) plays numerous roles in metabolic pathways involved in metabolic syndrome.

Objective:

In the search for susceptibility genes to metabolic syndrome, we hypothesized that common genetic variation in NR1H3 gene influences metabolic syndrome susceptibility.

Design:

Two large French population-based studies (n=1130 and 1160) including overall 664 individuals with and 1626 individuals without metabolic syndrome were genotyped for three polymorphisms (rs12221497, rs11039155 and rs2279239) of NR1H3.

Results:

We found that the −6A allele of rs11039155 was consistently associated with a 30% reduction in risk of metabolic syndrome in the two independent population samples (adjusted OR (95% CI)=0.68 (0.53–0.86), P=0.001 for the combined sample). Moreover, it was associated with an increase in plasma HDL-cholesterol concentrations (P=0.02 for the combined sample). Neither rs12221497 nor rs11039155, both polymorphisms located in the 5′ region of NR1H3, had significant influence on NR1H3 and ATP-binding cassette transporter A1 (ABCA1) gene expression in primary human macrophages.

Conclusions:

These results suggest that NR1H3 plays an important role in the HDL-cholesterol metabolism and in the genetic susceptibility to metabolic syndrome.

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Acknowledgements

The Lille and Toulouse MONICA population studies were supported by Grants from the Conseil Régional du Nord-Pas de Calais, ONIVINS, Parke-Davis Laboratory, the Mutuelle Générale de l'Education Nationale (MGEN), the Groupe Fournier, the Réseau National de Santé Publique, the Direction Générale de la Santé, the Institut National de la Santé et de la Recherche Médicale (INSERM), the Institut Pasteur de Lille and the Unité d'Evaluation du Centre Hospitalier et Universitaire de Lille. This study was part of the CRESCENDO (Consortium for Research into Nuclear Receptors in Development and Aging) consortium funded by the Commission's Sixth Framework Programme (integrated project LSHM-CT-2005-018652). We thank Dr Rébecca Dièvart and Lionel Helin for technical experiments.

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Authors and Affiliations

  1. INSERM, U744, Lille; Institut Pasteur de Lille, Lille; Université de Lille 2, UMR-S744,

    V Legry, D Cottel, T Deroide, P Amouyel & A Meirhaeghe

  2. Institut Pasteur de Lille, Lille, Lille, France

    V Legry, D Cottel, T Deroide, P Amouyel & A Meirhaeghe

  3. INSERM, U558, Toulouse; Faculté de Médecine,

    J Ferrières

  4. Faculté de Médecine, Toulouse, France

    J Ferrières

  5. Département d'Athérosclérose, Institut Pasteur de Lille, Lille; INSERM, U545, Lille; Université de Lille 2, Faculté de Pharmacie et Faculté de Médecine,

    G Chinetti & B Staels

  6. INSERM, U545, Lille, Lille, France

    G Chinetti & B Staels

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  1. V Legry
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  2. D Cottel
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  7. P Amouyel
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  8. A Meirhaeghe
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Corresponding author

Correspondence to A Meirhaeghe.

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Supplementary Information accompanies the paper on International Journal of Obesity website (http://www.nature.com/ijo)

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Legry, V., Cottel, D., Ferrières, J. et al. Association between liver X receptor α gene polymorphisms and risk of metabolic syndrome in French populations. Int J Obes 32, 421–428 (2008). https://doi.org/10.1038/sj.ijo.0803705

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  • DOI: https://doi.org/10.1038/sj.ijo.0803705

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