Liver X receptor gene polymorphisms and adipose tissue expression levels in obesity.
OBJECTIVE
LXRA and LXRB genes regulate adiposity, energy dissipation, as well as glucose and lipid homeostasis in mice. We investigated the LXR genes in human obesity.


METHODS
LXRA and LXRB mRNAs were quantified in abdominal subcutaneous adipose tissue of obese and nonobese women. The LXRA and LXRB genes were screened for polymorphisms and common single nucleotide polymorphisms genotyped in obese and nonobese women.


RESULTS
Relative LXRA mRNA expression levels were higher in obese women (P=0.03). One LXRA single nucleotide polymorphism, rs2279238, and one common haplotype, CAAGCC, as well as two LXRB single nucleotide polymorphisms, LB44732G>A and rs2695121, were associated with obesity phenotypes (nominal P values of 0.0075, 0.0014, 0.008 and 0.02, respectively). Furthermore, there was evidence of interaction between LXRA and LXRB alleles in determining body mass index.


CONCLUSIONS
Our results support a role for LXRA in human adipose tissue. The nominal associations of LXRA and LXRB alleles with obesity are interesting and should be further investigated in independent data sets.
Dahlman
Ingrid
I
Department of Medicine, Karolinska Institute, Huddinge, Stockholm, Sweden. Ingrid.Dahlman@medhs.ki.se
Nilsson
Maria
M
Jiao
Hong
H
Hoffstedt
Johan
J
Lindgren
Cecilia M
CM
Humphreys
Keith
K
Kere
Juha
J
Gustafsson
Jan-Ake
JA
Arner
Peter
P
Dahlman-Wright
Karin
K
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D000071518:Liver X Receptors; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D057093:Orphan Nuclear Receptors; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear