Gene Analysis and Treatment Optimization in Chinese Homozygous Familial Hypercholesterolemia

Study Overview
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Brief Summary
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Identify new or novel genes which may impact on cholesterol level, and establish the relationship between those gene mutations with atherosclerosis, as well as responses to lipid-lowering drugs.

Detailed Description
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To better understand the genetics basis for LDL-C elevation and develop an optimized lipid-lowering strategy, we propose to do the following studies: To establish a China HoFH registry, and collect DNA and blood samples from all available family members of each proband (pedigrees); To detect gene mutations known to cause FH and identify family suitable for future whole genome sequencing aimed to identify novel genes controlling cholesterol levels. 3.To establish the relationship between types of gene mutations and lipid and atherosclerosis profile, as well as responses to lipid-lowering agents.

Official Title
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The Study of Gene Analysis and Treatment Optimization in Chinese Homozygous Familial Hypercholesterolemia

Conditions
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Homozygous Familial Hypercholesterolemia

Intervention / Treatment
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* Genetic: Gene analysis
* Other: Historical data of lipid-lowering drug administration
* Other: Historical data of plasma lipids, xanthoma changes


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients of any age and sex who meet clinical or genetic criteria for hoFH as follows: Cutaneous xanthomata before the age of ten years LDLC > 13 mmol/L before treatment or > 7.76 mmol/L despite treatment Phenotypic features in keeping with HeFH in both parents Exclusion criteria: Inability of patient, or, if less than 18, a parent, to sign informed consent.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Homozygous Familial Hypercholesterolemia<br>Gene Analysis for Homozygous Familial Hypercholesterolemia cases | Genetic: Gene analysis<br>* Gene analysis<br>Other: Historical data of lipid-lowering drug administration<br>* Collecting historical data of lipid-lowering drug administration<br>Other: Historical data of plasma lipids, xanthoma changes<br>* Collecting historical data of plasma lipids and xanthoma changes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of LDLR Gene Mutations | Number of gene mutations based on the sequencing results in terms of some known genes and suspected novel genes. c.796 G>C and c.1048 C>T in the LDLR gene c.1448 G>A and c.1720C>A in the LDLR gene c.2030 G >A and c.1257 C>A in the LDLR gene homozygous mutation c.605 T>C in the LDLR gene | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C Reduction Percentage | plasma LDL-C reduction percentage with lipid-lowering drugs from pre-treatment to the last time follow-up time point plasma LDL-C reduction percentage calculation: plasma LDL-C at pre-treatment time point minus plasma LDL-C at the last time follow-up time point, and then compared with plasma LDL-C at pre-treatment time point, namely plasma LDL-C reduction percentage. | pre-treatment and 6-13 years post treatment |