In this study, we found that in Han population, LXRα A allele increased the risk of CHD. This result was consistent with LXRα physiological role in the human body. LXRα can regulate many target genes involved in lipid uptake, spillover and lipid metabolism. The regulation function of activated LXR α was as follows: 1) it can mediate the binding and transporting factor Al (ABCAl), ABCGl, ABCG5, ABCG4, ABCG8 located in the human macrophages and small intestine target genes ATP to promote endogenous lipid membrane transport; 2) it can activate human macrophages Niemann - Pick Cl protein (NPCI) and C2 protein (NPC2) to promote cholesterol transport from endosomes chamber to the cytoplasmic membrane; 3) it can promote receptor ApoE, ApoC-I, C-II, C-IV expression which were in charge of regulating the cholesterol outflow in adipocytes and macrophages; 4) it can control the liver and macrophages regulating enzymes such as phospholipid transfer protein (PLTP), lipoprotein lipase (LPL) remodeling lipoproteins. Meanwhile LXR α can inhibit many inflammatory cytokines and the expression of chemokines[14–18]. All these indicated that LXR α signaling pathway played an important role in the development of atherosclerosis. The mice tests also proved this view, the synthesis of liver X receptor agonist can inhibit the development of atherosclerosis, and the effects may be due to regulation of the underlying metabolic and inflammatory gene expression[19, 20].
Our studies suggested that in Chinese Han patients with CHD, the LXRα A allele frequency was significantly higher than that in the healthy population, A allele carries had 0.8 times increased risk of CHD (OR = 1.81). In the multivariate Logistic regression analysis, after the adjustment of age, sex, cholesterol, fasting glucose, hypertension, diabetes, smoking history and other confounding factors, A allele was still a risk factor of CHD independent of other traditional risk factors (P <0.05) which indicated that this locus had significantly increased risk for CHD. A recent study indicated that in the female population, LXR α polymorphism was significantly correlated with BMI and HDL-C concentration. In a French-Canadians population, the serum cholesterol levels in A allele carriers were higher than those in GG homozygotes carriers. The dietary cholesterol intake and this locus polymorphism had the combined effects on plasma TC and LDL-C levels suggesting that the plasma lipoprotein concentrations were not only associated with dietary cholesterol, but also regulated by LXR α gene expression. This locus was in recognition area of LXRα gene transcription factor and was involved in LXRα transcriptional regulation. In the present study, we did not find significant differences in lipids and BMI between A allele carriers and GG homozygotes carriers. This suggested that there may exist heterogeneity between different ethnics and populations, the diet and racial and body size differences between Han population and Caucasian may also be an explanation.
There were several limitations in our study. Firstly, the relative small sample size may reduce the statistics power and overestimate the OR value. Secondly, in the present study, we only investigated one SNP in LXRα gene. Although many previous studies suggested this SNP was associated risk factors of CHD, this SNP may not figure out the relationship between LXRα polymorphism and serum lipids and CHD risk. Finally, we only investigate this association in one case-control study, another independent case-control study for verification was not designed.