Category: Lipids/CV Health

Monitor: 24

24 - Genetic and clinical characteristics of patients with Familial Hypercholesterolemia: Data from a single centre in Singapore

Thursday, Apr 25
11:00 AM – 11:30 AM

Objective :

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by the presence of high plasma low density lipoproteins cholesterol (LDL-c). The aim of the study was to assess the heterogeneity, association of LDL Receptor mutations in patients, clinically diagnosed with FH in Singapore.


Methods : During the period of June 2015 to October 2018, patients (probands) with untreated/highest on-treatment LDLC>4.9mmol/l were recruited. DNA was extracted and Next Generation Sequencing (NGS) was performed in 26 lipid-related genes, including LDLR, APOB and PCSK9 and validated using Sanger. Multiplex-ligation probe analyses (MLPA) for LDLR were performed to identify large mutation derangements


Results :

Two hundred and five probands were recruited, with 72.5% males. Their mean age was (37.0±14.4) years.There were 67.3% Chinese (n=138), 17.6 % Malay (n=36) and 10.2% (n=21) Indians. 34.1% (n=70) of patients had LDLR mutations and five patients (2.3%) had APOB mutations. . 


Mean age at recruitment for people with LDLR Mutation was 30.7±13.2,compared to 40.6±13.9 for  those without LDLR Mutations.Total Cholesterol levels for Patients with LDLR mutations, versus APOB mutation versus no mutation: [(8.56±1.53) vs (6.93±0.76) vs (7.53±1.71)]mmol/l, p=0.008. LDL-C levels for Patients with LDLR mutations, versus APOB mutation versus no mutation: [(6.87±1.45) vs (5.29±0.76) vs (6.87±1.45)] mmol/l, p<0.001. Mean Fasting Triglyceride level in peope with LDLR mutation was 1.29 mmol/l compared to 1.72 mmol/l in people without LDLR mutations.
With respect to treatment, 24.5% and 7.9% of patients with LDLR mutations were on high intensity statins and Ezetimibe compared to 18.6 and  3.8% in the group with no LDLR mutations.
The prevalence of Type 2 diabetes (T2D) in people without mutations vs those with LDLR mutations (16.2% vs 4.3%, p=0.034). Prevalence of Systemic hypertension in 2 group was (22.3% vs 4.3%, p=0.005) .
The most common mutation was in LDLR exon 12 [c.1747C>T, p.(His583Tyr)]. There were 11 compound heterozygous mutations.


Discussion :

Patients with LDLR mutations were younger have statistically significant raised LDL cholesterol levels compared to those without mutations or with APOB mutations.
The prevalence of Type 2 Diabetes and Systemic Hypertension were found to be more commoner in peoplw without LDL R mutations.


Conclusion :

Patients with LDLR mutations had significantly higher cholesterols compared to those with APOB mutations and those without mutations detected. The commonest mutations detected in our cohort has also been reported from East Asia but different to ones reported from Europe.

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Sanjaya UDENI. Dissanayake

Consultant Endocrinologist
Khoo Teck Puat Hospital,Yishun Central,Singapore 768828
Singapore, Singapore

Dr. Sanjaya Udeni Dissanayake
MBBS(Sri Lanka); MD (Colombo); MRCP (U.K.); FRCP (Lond); FRCP (Edin)


Consultant Physician in Diabetes and Endocrinology/ GIM.

My special Interests Lipidology, Metabolic medicine, Management of Thyroid & Parathyroid disorders, Management of Endocrine disease in pregnancy
Personal Details


Name Dr. Sanjaya Udeni Dissanayake

Email: Dissanayake.sanjaya@alexandrahealth.com.sg


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Date of CCT(UK) (GIM/Diabetes/Endocrinology) 17/09/2010

Educational Qualifications

01/07/04
Member of Royal College of Physicians – United Kingdom (MRCP)


01-09-1998 MD General Medicine - University of Colombo, Sri Lanka

Examination conducted by the Postgraduate Institute of Medicine, University of Colombo Sri Lanka in conjunction with the Royal College of Physicians - UK

1-12-1990 MBBS (2nd Class Honours) - University of Peradeniya, Sri Lanka


Memberships of Professional Organisations
• Endocrine and Metabolic Society of Singapore-Committee member
• Royal College of Physicians of London
• Royal College of Physicians of Edinburgh
• European Society of Endocrinology
• American Association of Clinical Endocrinologists
• European Atherosclerosis Society
• International Atherosclerosis Society•

Current Job

3-10-14 to Date- Consultant Physician - Diabetes, Endocrinology/GIM
Khoo Teck Puat Hospital, Yishun Central, Singapore
My duties include

• In patient management of medical patients including problems related to Diabetes and Endocrinology.
• providing specialty input to acute Diabetes & Endocrine admissions
• Liaise with Diabetes team regarding multidisciplinary care for patients with Diabetes
• Providing specialty input for endocrine & metabolic problems and organizing O P care
• Weekly Multi-disciplinary Diabetes clinics
• In patient input to endocrine related Hospital admissions
• Weekly Medical & Endocrine clinics
• Multidisciplinary Lipidology outpatient clinics
With special interest in Familial Hypercholesterolemia, taking a leading role in setting up Singapore Familial Hypercholesterolemia Registry.
• Teaching and mentoring Diabetes and Endocrinology specialty trainees

Other duties/Involvements
• Supervising junior Medical staff (HO/MO) & Registrars•
• Active involvement in Teaching & training Medical students –Clinical Senior Lecturer for Yong Loo Lin School of Medicine attached to National University of Singapore (NUS) and clinical tutor attached to Lee Kong Chiang school of medicine
• Ongoing research Project to study Genetics of Familial Hypercholesterolemia
•. Active involvement in collaborative work related to Singapore Familial Hypercholesterolemia Registry

Sharon Pek Li Ting

Principal Research Officer
Clinical Research Unit, Khoo Teck Puat Hospital

Dr Sharon Pek graduated from National University of Singapore with a PhD from Department of Pathology in 2011. She began her post-doctoral research in Obesity, Diabetes and Lipid disorders in 2010 in Khoo Teck Puat Hospital. Her interests are in genetic and protein biomarkers in these metabolic diseases. Dr Sharon has also received independent grant support for her research work in these areas and has authored and co-authored numerous peer-reviewed journals. Dr Sharon is a co-Investigator in several national grants with her colleagues, with a major focus on Diabetic foot complication (neuropathy and peripheral arterial disease). Recognizing her efforts, Dr Sharon has also won Young Investigator Awards in 2016 and 2018 for her presentations in national congresses.

Wenyi Wan

Research Nurse
Clinical Research Unit,Khoo Teck Puat Hospital

Wenyi graduated with Bachelor in Nursing. She is now a clinical Research Nurse attached to Familial Hypercholesterolemia Project

Fariha Bte Siraj

Research Assistant
Clinical Research Unit,Khoo Teck Puat Hospital

Fariha graduated with a Diploma in Biomedical Research. She is currently a Research Assistant for Familial Hypercholesterolemia study Khoo Teck Puat Hospital site and pursuing her Bachelor degree in Biomedical Science.

Eric Chan Zit Liang

Research Officer
Clinical Research Unit,Khoo Teck Puat Hospital

Eric graduated with a BSc (Hons). He is now a Research Officer Attached to Clinical Research Unit, Khoo Teck Puat Hospital

Michelle Lin Xueqin

Research Officer
Clinical Research Unit,Khoo Teck Puat Hospital

Michelle graduated with a BSc from University of Queensland. She is now a Research Officer attached to Clinical Research Unit, Khoo Teck Puat Hospital

Justin Tang I-Shing

consultant cardiologist
Khoo Teck Puat Hospital

MBBS (Singapore) MRCP (UK) PhD (Edinburgh) is a consultant cardiologist at Khoo Teck Puat Hospital, with a special interest in cardiometabolic diseases.

Su Chi Lim

Director Clinical Research Unit
Clinical Research Unit-Khoo Teck Puat Hospital ,Diabetes Centre- Admiralty Medical Centre

A/P Lim graduated from National University of Singapore with an MBBS and a PhD in 2010. He is currently a Director,Clinical Research Unit-Khoo Teck Puat Hospital ,Senior Endocrinologist and Deputy Director-Diabetes Centre- Admiralty Medical Centre.Special research interests include Diabetic Kidney Disease and Genetics in Diabetes including MODY

Chee Fang Sum

Senior Consultant Endocrinologist
1Department of Medicine, Division of Endocrinology, Khoo Teck Puat Hospital Clinical Research Unit, Khoo Teck Puat Hospital, Diabetes Centre, Admiralty Medical Centre

A/P Sum graduated from National University of Singapore with an MBBS, He is currently a Senior Consultant Endocrinologist attached to Diabetes Centre, Admiralty Medical Centre.

Subramaniam Tavintharan

SeniorConsultant Endocrinologist
Head,Diabetes Centre, Admiralty Medical Centre

A/P Tavin graduated from National University of Singapore with an MBBS and Masters in Clinical Research. He is currently a Senior Consultant Endocrinologist with Special interest in Lipid disorders.Chief coordinator for the Singapore Familial Hypercholesterolemia Project.Director, Diabetes Centre, Admiralty Medical Centre

S M S Ayesha

Jesssie Fong