This document discusses a study assessing the relationship between vitamin D receptor (VDR) gene polymorphisms at the FokI site and hepatocellular carcinoma (HCC) in chronic liver disease patients. The study used PCR and RFLP techniques to analyze DNA samples from patients. Results found a cytosine to thymine substitution and three electrophoretic profiles. The conclusion is that VDR FokI polymorphisms may help identify severity of HCC for patients infected with HCV, as low vitamin D levels are associated with increased liver injury. However, the polymorphism shows no clear prognostic relationship with clinical features of HCC.

1. ISAAC TOBON ZAPATA
SEMESTRE III
ESCUELA CIENCIAS DE LA SALUD-FACULTAD DE MEDICINA
UNIVERSIDAD PONTIFICIA BOLIVARIANA

2. INTRODUCTION:
Vitamine D and Hepatocellular carcinoma FokI polymorphism
• The Vitamin D receptor (VDR) has been viewed as
an essential part of genetic cancer research. The
VDR binds to the biologically active form of vitamin
D and induce a lot of cell functions.
• The Hepatocellular carcinoma is associated with the
condition of hepatitis C virus infection, Which
produces liver cirrhosis and development of HCC.
• The FokI is an independent polymorphic site in the
VDR gene with thymine (T) to cytosine (C)
substitution in the start codon ATG, affecting the
structure and the function of the encoded protein.

3. OBJECTIVE
To assess the relationship between vitamin D receptor (VDR) gene
polymorphisms at FokI site and hepatocellular carcinoma (HCC) in
chronic liver disease patients.
Tomado de: http://www.chilegenomico.cl/2016/04/26/entrevista-a-dra-luisa-herrera-chilegenomico-el-estudio-de-nuestra-genetica-por-medio-del-analisis-de-
polimorfismo-de-nucleotido-simple-snps/---https://www.slideshare.net/ivancev/vitamina-d-y-alergia-conferencia-del-dr-ortega-martell-en-cmica-2016

4. Materiales y métodos:
• Selección de pacientes:

5. MATERIALES Y MÉTODOS:
• Amplificación del gen VDR por reacción en cadena de la polimerasa (PCR):
El fragmento del gen VDR, que contiene el sitio polimórfico FokI con una
sustitución de C> T, se amplificó por PCR.
La PCR depende de una ADN polimerasa termoestable,
la Taq polimerasa, y requiere de cebadores de ADN diseñados
específicamente para esta región de ADN de interés.
Se pueden obtener muchas copias de ADN in vitro del
fragmento del gen VDR.
Tomado de: https://es.khanacademy.org/science/biology/biotech-dna-technology/dna-
sequencing-pcr-electrophoresis/a/polymerase-chain-reaction-pcr

6. • Restricción de fragmentos largos polimórficos
(RFLP):
Determinación de polimorfismos a través
del corte de fragmentos de ADN usando
enzimas de restricción
Permiten obtener Perfiles electroforéticos
Se obtuvo el polimorfismo del
gen VDR a través de una enzima
de restricción FokI específica.
Tomado de: http://www.wikillerato.org/Enzimas_de_restricci%C3%B3n.html

7. La ausencia del sitio de restricción fokI (265 pb) se asignó
como un alelo común f (alelo de tipo salvaje)
Los genotipos FokI se asignaron como homocigotos para el
alelo FF (CC nucleótidos) y homocigoto para el alelo ff
(nucleótidos TT). La presencia de 265, 196 y 69 pb se asignó
como heterocigoto Ff (CT nucleótidos).
Análisis de PCR-RFLPs y determinación de
genotipos.

8. RESULTADOS:
Sustitución de citosina por timina
Proteína anómala
Figura 1

9. FIGURA 2
DNAs que no están cortados por la
enzima de restricción.
265 bp --- Marcador de
peso molecular del gen
VDR.
3 perfiles electroforéticos

10. Tablas de resultados:

12. DISCUSION
Author
Yao et al.
Concept
There isn´t any prognostic association
relationship of the VDR FokI with the
clinical feature of HCC as tumor stage,
tumor differentiation, presence of
cirrhosis, and lymph node metastasis
Yes or not
Falleti et al. It was studied the association between VDR
gene polymorphisms and hepatocellular
carcinoma in alcoholic cirrhosis population
and found the FokI C > T polymorphism was
non-significantly distributed between HCC
and non HCC patients
Scalioni et al. found in Brazilian patients with chronic liver
cirrhosis due to HCV a strong association between
vitamin D sufficiency and the carriage of the VDR
mutant allele FokI TT genotype; a situation that
could postulate that, FokI C > T polymorphisms may
be used to signal the severity of HCC in those
infected with HCV since low concentrations of
vitamin D were found to be directly associated with
increased liver injury

13. CONCLUSIONS
The genetic polymorphisms represent a great number of
variations between the different ethnic groups and populations
around world, and these polymorphisms reveal the importance
of always knowing what is the race, culture and demographic
origin for the treatment of each of our patients
Thanks to these studies, it is possible to have a better
focus on the diagnosis, time treatment and
prevention methods of a endless number of diseases
that will allow us to give a better quality of life for
more people.
Tomado de: https://www.cancerresearchuk.org/about-cancer/what-is-cáncer--
https://programacionavan.wordpress.com/2014/06/10/polimorfismo-genetico/