Liver X receptor beta (LXR?) is a member of the nuclear hormone
receptor superfamily which modulates transcription of many target genes involved
in cholesterol, lipid and carbohydrate metabolism (1-3). This ligand-dependent transcription
factor is encoded by the nuclear receptor 1 type H2
(NR1H2) gene located on chromosome 19
and is ubiquitously expressed at moderate to high levels in almost all tissues (4). The transcriptional activity of LXR? is
depended on the exposure of oxidized cholesterol
and subsequent heterodimerization with the retinoid X receptor
(RXR). Activated LXR–RXR heterodimers promote adipogenesis
and lipid accumulation in adipocytes by transcriptional regulation of
sterol regulatory binding transcription factor 1 (SREBP1C), the master
regulator of TG synthesis, and several target genes including FAS and stearoyl-CoA
desaturase 1 in the SREBP1C pathway (5-8).
The lipogenic actions of LXRs have presented them as potential
pharmaceutical targets for the treatment of metabolic disorders such as
diabetes, metabolic syndrome, obesity, and atherosclerosis (9). Targeted
disruption (knockout) of the LXR? gene in mice have revealed a strong
association with defects in the cardiovascular system, homeostasis and
metabolism and the nervous system (10).
Based on having an important role in regulating the
lipid and carbohydrate metabolism, genetic variations
in LXR? may contribute in mediating
susceptibility to obesity and modulating serum lipids and glucose levels.
One of the common variation within the NR1H2
gene is rs2695121, which is identified by C
to T substitution in intron 2. This SNP was associated with several metabolic-related
disorders including high blood pressure, metabolic syndrome, type 2 diabetes
and also preeclampsia (11-13). A 2006
study by Dahlman reported
evidence of the association between LXR?
rs2695121 polymorphism and obesity phenotypes (13).
Whereas, other subsequent reports have been inconsistent (14). However, no reported data exists for the
association of this SNP with the risk of obesity and related
metabolic traits in Iranian population. Based
on the proposed involvement of LXR? in the regulation
of lipid and carbohydrate homeostasis, the
present cross-sectional study was designed to assess
the potential association of LXR? rs2695121 variant with obesity and
related metabolic traits in a northeastern Iranian