Liver X receptor gene polymorphisms and adipose tissue expression levels in obesity.
Dahlman I., Nilsson M., Jiao H., Hoffstedt J., Lindgren CM., Humphreys K., Kere J., Gustafsson J-A., Arner P., Dahlman-Wright K.
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. CONCLUSION: 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.