Homozygous Familial Hypercholesterolemia
Conditions
Brief summary
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
To better understand the genetics basis for LDL-C elevation and develop an optimized lipid-lowering strategy, we propose to do the following studies: 1. To establish a China HoFH registry, and collect DNA and blood samples from all available family members of each proband (pedigrees); 2. 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.
Interventions
GENETICGene analysis
Gene analysis
OTHERHistorical data of lipid-lowering drug administration
Collecting historical data of lipid-lowering drug administration
OTHERHistorical data of plasma lipids, xanthoma changes
Collecting historical data of plasma lipids and xanthoma changes
Sponsors
Central South University
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of LDLR Gene Mutations | 1 year | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LDL-C Reduction Percentage | pre-treatment and 6-13 years post treatment | 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. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients of HoFH patients of Homozygous Familial Hypercholesterolemia | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Patients of HoFH |
|---|---|
| Age, Continuous | 5 year STANDARD_DEVIATION 1 |
| plasma LDL cholesterol concentration | 17.55 mmol/L STANDARD_DEVIATION 2.34 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
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
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HoFH Patients | Number of LDLR Gene Mutations | 7 gene mutations |
Secondary
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.
Time frame: pre-treatment and 6-13 years post treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HoFH Patients | LDL-C Reduction Percentage | 48.16 percentage of plasma LDL-C reduction | Standard Error 8.5981 |