Abstract 9314: Clinical Impact of Heterozygous Carrier of ATP-binding Cassette Sub-family G Member 5 Gene on Asymptomatic Normolipidemic Patients: Evidence From Familial Gene Analysis

Abstract

Background: Sitosterolemia is a rare recessive form of inherited disease characterized by increased levels of plant sterols such as sitosterol, the cause of which is ATP-binding cassette (ABC) sub-family G member 5 (ABCG5) or ABCG8 gene mutations. However, few data exist regarding the clinical features and significance of heterozygous sitosterolemic carrier due to the rarity of this disease. The aim of our study was to determine the clinical impact of heterozygous mutation carriers of ABCG5 or ABCG8 gene. Methods and Results: We performed genetic analyses of ABCG5 and ABCG8 genes for the 15 family members of patients with homozygous sitosterolemia from different 3 families, and investigated their serum sitosterol levels as well as their lipid levels. We identified 12 heterozygous carriers (male=6, mean age=40) which exhibit single mutation in ABCG5 gene among these families (c.130C>T, c.1306G>A, c.1813_1817delCTTTT) as well as 3 normal family members (male=1, mean age=48). Although there were no significant differences in TC, TG, HDL-C, and LDL-C levels between heterozygous carriers and normal family members, serum sitosterol level of heterozygous carriers was significantly higher than that of normal family members (10.8±4.3 vs 2.7±0.5 μg/ml, p<0.05). Interestingly, heterozygous carriers showed neither xanthomas nor any coronary artery diseases. Conclusions: These results demonstrate that heterozygous ABCG5 gene mutation carriers which are somewhat difficult to be identified by the conventional methods may exist among the common normolipidemic patients without significant clinical manifestations. We suggest that the functional analysis of ABCG5 or ABCG8 may facilitate identifying hyper sitosterolemic carriers.