Low Density Lipoprotein - Receptor (LDL-R) Gene Mutations among Filipinos with Familial Hypercholesterolemia
スポンサーリンク
概要
- 論文の詳細を見る
Background: Familial Hypercholesterolemia (FH) is an autosomal dominant disease resulting from mutations of the LDL (LDLR) receptor gene leading to a diminished catabolism and elevated level of LDL cholesterol (LDL-C). It is associated with an increased risk for cardiovascular disease (CVD). The MEDPED (Make Early Diagnosis-Prevent Early Death) program, an initiative cited by the WHO Human Genetics Programme in their report on FH, initiated international collaboration to identify and follow-up patients with FH globally. From Asia-Pacific, only 6 countries are participating and no data among Filipinos particularly on genetic profiles is available at present. This study attempts to initiate data collection and participation in the global initiative.<BR>Objectives:<BR>Primary: 1. To describe the phenotype of Filipino patients with FH.<BR> 2. To determine and characterize the LDL-R gene mutations among Filipino patients with clinical features of FH<BR>Secondary: To determine the association of the clinical characteristics of FH with the presence of LDLR gene mutations <BR>Design: Cross- Sectional Study<BR>Setting: Multicenter, Outpatient Clinic<BR>Participants: 60 unrelated patients, 18 y/o and above from <I>UP-PGH</I>, <I>Manila Doctors Hospital and Cardinal Santos Medical Center</I>. FH was dignosed according to the Dutch Lipid Clinic Network Criteria cited by WHO which is based on a history of premature CVD, family history, tendon xanthoma, arcus cornealis, and LDL C levels.<BR>Methods: With informed consent, clinical history, physical examination and lipid profile data were determined. Blood samples were extracted, processed to isolate DNA specimens at the <I>National Institutes of Health, Institute of Human Genetics</I>, and sent to <I>Canterbury Health Laboratories at Christchurch, New Zealand</I> for DNA analysis.<BR>Analysis: Descriptive statistics, Fisher's exact test and Student's <I>t</I>-test using Stata version 6.0 software.<BR>Results: Sixty patients with a mean age of 55 y/o were included, including 39 (65%) females. The mean LDL level was 227 mg/dl. Cardiovascular Disease and a family history of dyslipidemia were present in 55 & 60% of the samples, respectively. Twenty percent had documented LDL-R gene mutations. Six of the mutations were considered novel. A family history of dyslipidemia, an elevated LDL-C level, and a high FH score exhibited a statistically significant association with mutations.<BR>Conclusion: The study population has a high prevalence of CVD at an average age of 55 years with a strong family history of dyslipidemia and very high average LDL-C levels. One out of every 5 patients had LDL-R gene mutations, 6 of which were considered novel. LDL-R gene mutation was significantly associated with family history of dyslipidemia, LDL-C Level and FH score.<BR>Clinical and Research Implication: This is the first international collaborative genetic study among Filipinos with FH. Data could allow the country to participate in the WHO/MEDPED global program. Collaborative efforts will lead to more effective detection, treatment and prevention of CV events. Novel mutations were discovered and further analysis of these genes will be done.
- 一般社団法人 日本動脈硬化学会の論文
一般社団法人 日本動脈硬化学会 | 論文
- Effects of Lysosomal Protease Inhibitors on the Degradation of Acetylated Low Density Lipoprotein in Cultured Rat Peritoneal Macrophages
- Genomic Structure and Mapping of Human Orphan Receptor LXR Alpha : Upregulation of LXRa mRNA During Monocyte to Macrophage Differentiation
- The Gene Expression Profile of Human Umbilical Vein Endothelial Cells Stimulated by Tumor Necrosis Factor a Using DNA Microarray Analysis
- Participation of T Lymphocytes and Macrophages in Atherogenesis
- Immunohistochemical and Quantitative Analysis of Cellular and Extracellular Components of Aortic Atherosclerosis in WHHL Rabbits