A Novel 11-Basepairs Deletion Variant In The Promoter Region Of Scavenger Receptor Class B Type ? Gene(SCARB1) Associated With The Plasma HDL Cholesterol Levels And Coronary Heart Disease Risk In Chinese Han Population

Aims:To investigate impact of polymorphisms in the promotor region Scavenger Receptor Class B Type ? Gene(SCARB1)on the plasma lipid levels and risk of coronary heart disease(CHD)in Chinese Han population.Methods and Results:By resequencing 48 randomly selected individuals we found a 11-basepairs-deletion variant in-118 to-128 region in SCARB1(minor allele frequecne=0.018).Luciferase activity assays demonstrated that-118 to-128del resulted in about 30%reduction of transcription activity in HepG2 and LO2 cells and furthermore,electrophoretic mobility-shift assay detected-118 to-128del destroyed the binding site of Spl.Genetic association studies in a general population containing 3856 individuals found that-118 to-128del carriers had higher levels of HDL-c than had noncarriers(1.52 ± 0.65 vs.1.28 ± 0.52 mmol/L,P=0.038).After genotyping-118 to-128del in 1924 cases of coronary heart disease and 1950 controls and then replicated our study in additional independent case-control cohorts comprising of 1930 cases and 1595 controls.Results showed that-118 to-128del was significantly associated with increased risk of CHD(discovery set:odds ratio(OR)= 1.48,P=0.02;replication set:OR=1.36,P=0.03).Conclusions:The polymorphism-118 to-128del of promoter region of SCARB1 increases the levels of HDL-c and consequently,risk of CHD in Chinese Han population.Our results did not support that HDL-c levels play the causal role in CHD...