Methylation mechanism of the expressional difference of low-density lipoprotein cholesterol in familial hypercholesterolemia patients with same gene mutation
Wu Wenfeng
Sun Liyuan
Wen Wenhui
Wu Yue
Wang Luya
Abstract：Objective To investigate the mechanism of the expressional difference of low-density lipoprotein cholesterol(LDL-C) in familial hypercholesterolemia(FH) patients with low-density lipoprotein receptor(LDL-R) gene A606T mutation. Methods Ten heterozygous patients with FH diagnosed by clinical manifestations and genetic detection in Beijing Anzhen Hospital,Capital Medical University from January 2016 to March 2017 were divided into high LDL-C group (LDL-C≥5 mmol /L,6 cases) and low LDL-C group (LDL-C < 5 mmol /L,4 cases). DNA methylation of CpG island in peripheral blood was detected by the Illumina Human Methylation 850K BeadChip. Expressions of mRNA and protein of the differential gene were determined by real-time fluorescence quantitative polymerase chain reaction(RT-PCR) and enzyme linked immunosorbent assay(ELISA). Results Genome-wide methylation screening showed that cholesterol-7α-hydroxylase (CYP27A1 ) gene was hypermethylated in the high LDL-C group. RT-PCR and ELISA revealed that CYP27A1 mRNA and protein expression in the high LDL-C group were significantly lower than those in the low LDL-C group[(0.041 ± 0.013) vs (1.011 ± 0.076) ,(136 ± 12) μg /L vs (174 ± 26) μg /L](both P < 0.05). Conclusion FH patients with LDL-R A606T mutation have low expressions of CYP27A1 mRNA and protein,which is related with its hypermethylation; the abnormal methylation of CYP27A1 gene may be involved in lipid metabolism in FH patients.
Keywords：Familial hypercholesterolemiaDNA methylationLow-density lipoprotein
Publication Date：2019-01-01
Online Publishing Date：2026-09-14(First online date of this platform, not the publication date of the document)
Pages：3( 723-725 )