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


METHODS
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.
Legry
V
V
INSERM, U744, Lille, France.
Cottel
D
D
Ferrières
J
J
Chinetti
G
G
Deroide
T
T
Staels
B
B
Amouyel
P
P
Meirhaeghe
A
A
D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005602:France; D008040:Genetic Linkage; D006801:Humans; D000071518:Liver X Receptors; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D057093:Orphan Nuclear Receptors; D020641:Polymorphism, Single Nucleotide; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012306:Risk
D008076:Cholesterol, HDL; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear