Nutrigenomics and Familial
Hypercholesterolemia
Andréa Simões 1, Cláudia Azoia 1, Dulce Rodrigues 1, Tatiana Cunha 1, Célia A. Gomes 2
Edição 02/14
1 Dezembro 2014
(1) – Alunos do 3º ano da Licenciatura de Dietética e Nutrição da Escola Superior de Tecnologia da Saúde de Coimbra
(2) – Docente de Genética da Escola Superior de Tecnologia da Saúde de Coimbra
1. Introduction
Familial Hypercholesterolemia (FH) is an hereditary disease
45Y
C:318
2
3
64Y
C:241
60Y
C:233
20 000
individuals
with FH
56Y
C:335
AMHA:52Y
from a genetic alteration, which causes an increase in cholesterol levels, specifically
LDL Cholesterol (LDL-C)1,2. This is considered as a risk factor for the premature
development of cardiovascular disease (CVD)1,2. It is an autosomal dominant disease,
40Y
C:375
2
3
37Y
C:199
33Y
C:188
Legend
29Y
C:303
35Y
C:421
Y – Age in years
which their genotype may be heterozygous or, more rarely, homozygous, with the
C – Cholesterol with respective values
AMHA – Acute Myocardial Heart Attack
latter more severe phenotype and Total Cholesterol (TC) levels higher than in the
heterozygous form1,2.
7A
C:502
4A
C:164
Fig.1- Family tree of FH carrier family.
Our main goal is to demonstrate the relationship between bioactive compounds (in particularly, polyphenols) and the expression of some genes that are "altered" in
the individual with FH.
2. Familial Hypercholesterolemia
4. Nutrigenomics and FH
The FH is considered a "silent disease" since usually has no symptoms3.
Diagnosis
TC > 290 mg/dl
ou c-LDL
>190mg/dl
Tendon
Xanthomas
Table 2: Dietary polyphenols with target protein and molecular signature9
Molecular
Signature
Dietary Polyphenols
Target Protein
Procyanidin B2, Procyanidin
C1, Cinnamtannin A2,
Resveratrol, Catechin,
Epicatechin, Quercetin, Gallic
acid, Tangeretin, Taxifolin
APOA-I, APOB,
APOB100
Increase
expression and
secretion
Catechin, Naringenin,
Hesperetin, Gossypin,
Eriocitrin, Red grape juice
polyphenols
LDLR
Increase
expression
TC - Total Cholesterol
Mutations in
LDLR, APOB or
PCSK9 genes
This disease can be caused by a mutation in the receptor gene of low
density lipoproteins (LDLR) or apolipoprotein B gene (APOB) or the
proprotein convertase subtilisin / kexina type 9 gene (PCSK9)2,5.
3. Genetics of FH
5. Nutritional and pharmacological care of FH
Table 1: Genetic causes that cause HF 2,5-8
LDLR gene
Chromosome
Chromosome
19p13.1-p13.3
ApoB gene
Chromosome
2p23-p24
PCSK9 gene
Chromosome
1p32-p34
Encodes
Mutations
Class 1
Class 2
Class 3
Class 4
Class 5
LDL receptor - cell
surface
glycoprotein
(LDLR)
ApoB100 protein
(LDL binds to its
receptor through
apoB100)
(+ frequent in Europe)
Serine protease
(decreased LDLR
in hepatocytes)
Increased activity
(increased levels of cLDL)
p.R3531C
p.R3527Y
p.R3527Q
Individuals suffering from FH should adopt a healthier life style combined
with a balanced diet2 :
Rich in plant foods, fruits, whole grains and fiber, (preferably
soluble since it helps to decrease the concentrations of TC and cLDL5
Low in saturated and trans fat, preferring the unsaturated
(mono and polyunsaturated), in particular the olive oil, to
reduce the c-LDL from the diet5
Drug therapy is almost inevitable, and is a therapy that involves
the medication with statins, fibrates, nicotinic acid and
cholestyramine1,2.
5. Final Remarks
Early diagnosis enables that CVD risk behaviours (like physical inactivity, smoking, alcohol) be reduced by implementing physical activity and healthy eating habits
(such as diet low in saturated fats and quickly absorption sugars) and / or pharmacological treatment, thus modifying the levels of mortality and morbidity.
6. References
1.Bourbon M, Rato Q. Portuguese Familial Hypercholesterolemia Study: presentation of the study and preliminary results. Rev. Port. Cardiol. 2006;25(11):999-1013.
6.http://vega.sanger.ac.uk/Homo_sapiens/Location/Chromosome?chr=19;r=19:1-58617616, consultado a 18/11/2014
2.Ana Isabel da Costa Freitas Caracterização Bioquímica e Molecular da Hipercolesterolemia Familiar na Região Norte e Centro de Portugal. 2010
7.http://vega.sanger.ac.uk/Homo_sapiens/Location/Chromosome?r=2%3A1-1000, consutado a 18/11/2014
3.http://fhportugal.pt/o-que-e-a-fh/, consultado a 18/11/2014
4.Gaspar I. Hipertecolesterolemia familiar . Do diagnóstico à prevenção cardiovascular . A propósito de um estudo holândes
8.http://vega.sanger.ac.uk/Homo_sapiens/Location/Chromosome?r=1%3A1-1000, consultado a 18/11/2014
5.Brasileira S. I Diretriz Brasileira de Hipercolesterolemia Familiar (HF). Arq. Bras. Cardiol. 2012;99(2):1-28 Brasileira S. I Diretriz Brasileira de Hipercolesterolemia Familiar
9.Rahman M, Rahman F, Fatima N, et al. SPECTRA OF ALTERNATIVE THERAPIES OF HYPERCHOLESTEROLEMIA BY DIETARY BIOACTIVES : EMPHASIS ON
(HF). Arq. Bras. Cardiol. 2012;99(2):1-28
NUTRIGENOMICS OF POLYPHENOLS. 2013;1(1):1-7.