Abstract 341: Impact of Common Variant of Farnesoid-X-receptor Gene on Cardiovascular Risk Factors
Objective: Many nuclear receptors play important roles in energy homeostasis, inflammation and development of atherosclerosis. Bile acid receptor FXR is shown to have crucial roles in cholesterol conversion into bile acids, and also in glucose metabolism. We identified common polymorphism of FXR gene in Japanese population, and hypothesized that this polymorphism could affect energy homeostasis.
Methods: All the coding regions of FXR gene were screened in 180 hyperlipidemic patients by PCR-DGGE analysis. Clinical characteristics were evaluated in 298 general males and in another 176 (50 diabetes and 126 non-diabetes) coronary artery disease suspected patients (CAD group) including 105 coronary angiography performed patients.
Results: We identified FXR -1g->t variants, and its allele frequency was 0.32. FXR -1t carriers had significantly higher BMI both in general males (23.2 ± 2.4 vs. 23.9 ± 2.7 kg/m2, p=0.03) and in non-diabetes CAD group (22.2 ± 4.2 vs. 24.2 ± 4.1 kg/m2, p=0.01). In lipid analysis of non-diabetes CAD group, FXR -1t carriers showed lower lipid levels both in HDL-C (57 ± 22 vs. 49 ± 14 mg/dl, p=0.03), and in LDL-C (159 ± 59 vs. 136 ± 57 mg/dl, p=0.03). With ultrasonography, FXR -1t carriers showed resistance to development of fatty liver (59% vs. 32%, p=0.02). Considering that bile acids had been shown to decrease both apolipoprotein AI and apolipoprotein B expression, and to improve hepatic steatosis with FXR activation in mice, our results suggested the increased function of FXR -1t variant.
Conclusion: Common genetic variant of FXR seems to have deep impact in energy homeostasis associated with cardiovascular risk factors. Whether this variant could affect long-term clinical course should further be sought.