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

Legry, Vanessa;Cottel, Dominique;Ferrières, Jean;Chinetti, Giulia;Meirhaeghe, Aline;et.al.
(2008) International Journal of Obesity — Vol. 32, n° 3, p. 421-428 (2008)

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Authors
  • Legry, VanessaUCLouvain
    Author
  • Cottel, Dominique
    Author
  • Ferrières, Jean
    Author
  • Chinetti, Giulia
    Author
  • Meirhaeghe, Aline
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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 alpha (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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Legry, V., Cottel, D., Ferrières, J., Chinetti, G., Deroide, T., Staels, B., Amouyel, P., & Meirhaeghe, A. (2008). Association between liver X receptor alpha gene polymorphisms and risk of metabolic syndrome in French populations. International Journal of Obesity, 32(3), 421-428. https://doi.org/10.1038/sj.ijo.0803705 (Original work published 2008)