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.
Objectives:
Primary: 1. To describe the phenotype of Filipino patients with FH.
2. To determine and characterize the LDL-R gene mutations among Filipino patients with clinical features of FH
Secondary: To determine the association of the clinical characteristics of FH with the presence of LDLR gene mutations
Design: Cross- Sectional Study
Setting: Multicenter, Outpatient Clinic
Participants: 60 unrelated patients, 18 y/o and above from UP-PGH, Manila Doctors Hospital and Cardinal Santos Medical Center. 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.
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 National Institutes of Health, Institute of Human Genetics, and sent to Canterbury Health Laboratories at Christchurch, New Zealand for DNA analysis.
Analysis: Descriptive statistics, Fisher’s exact test and Student’s t-test using Stata version 6.0 software.
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.
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.
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.