Test PNPLA3

Relationship of genetics with the liver

Liver diseases are caused by a variety of causes, the most important being infections by hepatitis B or hepatitis C viruses and steatosis. The severity and evolution of liver damage in these diseases depends not only on their causal agent and environmental factors (alcohol intake, diet, etc.), but also to a large extent on each individual’s genetics.

The Human Genome project has shown that there is 0.1% genetic variability among people. This variability is mainly due to polymorphisms of a single nucleotide (SNP of the English Single Nucleotide Polymorphism) that consist in the change of one nucleotide for another in the genome sequence, having been proven that many of these genetic polymorphisms may have pathogenic implications. In this way, it has been found that a polymorphism in the PNPLA3 gene is closely related to the severity of the liver injury. The study of this polymorphism helps to determine the risk of progression of the liver damage of each patient depending on the illness that he / she suffers.

Fatty Liver (Hepatic Steatosis)

Non-alcoholic fatty liver is a disease associated with overweight whose prevalence is increasing throughout the world, being currently considered the main cause of chronic liver disease. In western countries it is estimated that between 20% and 30% of the general population has an excessive accumulation of fat in the liver. This accumulation of fat in the liver (steatosis) can progress in about 30% of cases to more severe forms of liver damage with inflammation and fibrosis (steatohepatitis) and even cirrhosis and hepatocellular carcinoma.

Although obesity or type 2 diabetes are risk factors for the development and progression of this disease, in several studies it was found that genetic factors were also involved.

It has been shown that the polymorphism in the PNPLA3 gene is directly related to the susceptibility to suffering from non-alcoholic fatty liver and subsequently it has also been verified that the polymorphism in the PNPLA3 gene, which is analyzed in this genetic test, is an independent risk factor of progression to aggressive forms of the disease, including liver cirrhosis and hepatocellular carcinoma.

Hepatitis B

Chronic hepatitis B virus infection is associated with a broad spectrum of liver damage ranging from minimal damage to chronic active hepatitis that can progress to liver cirrhosis and hepatocellular carcinoma. The severity of liver damage is associated not only with factors specific to the virus, but also specific (genetic) characteristics of each individual, such as the propensity to accumulate fat in the liver or hepatic steatosis.

As mentioned, there is a polymorphism in the PNPLA3 gene that determines the risk of developing steatosis. The study of this polymorphism in patients with chronic hepatitis B has shown that it is associated with increased liver inflammation, the risk of developing severe steatosis and the appearance of iron deposits in the liver.

Hepatitis C

Chronic hepatitis C virus infection is associated with a broad spectrum of liver damage ranging from minimal damage to chronic active hepatitis, which in 20% progresses to liver cirrhosis and hepatocellular carcinoma. Among the factors that are associated with the progression of liver damage are age at the time of infection, genotype of the virus, alcohol intake, type 2 diabetes, etc. However, even taking into account all these factors, the progression of liver damage is not the same for all patients, which indicates the existence of characteristics of each individual (genetic factors) that are directly involved in this progression.

In recent years it has been shown that the same polymorphism of the PNPLA3 gene involved in the other diseases is associated with an increased risk of progression of liver injury in patients with chronic hepatitis C.

The genetic tests currently available already offer a useful clinical application.
Dr. Vicente Carreño

Frequently Asked Questions

Answers to questions about this technique

What does this Test provide?

Determine which people with risk factors (overweight, type 2 diabetes) have a greater chance of developing hepatic steatosis.
It identifies which patients with hepatic steatosis have a greater risk of progressing to more aggressive forms of the disease, including cirrhosis and hepatocellular carcinoma.
It identifies which patients with chronic hepatitis B or C have a higher risk of developing more severe liver damage.
It helps the doctor to determine the frequency of reviews, ultrasounds, elastographies, analytical, etc. depending on the results of the test.
The sample taken (a drop of blood from the fingertip or a saliva sample) is done in 2 minutes. It is not necessary that the patient is fasting because of what can be done at the time and in the consultation itself.
The results are delivered within a maximum period of two weeks.
Since it is a genetic test, you only have to perform this test once in your life, being able to do it at any age.

Who is it for?

People who due to their characteristics (overweight, type 2 diabetes, etc.) may be at risk of developing hepatic steatosis.
Patients diagnosed with hepatic steatosis.
Patients with chronic hepatitis B or C.
For relatives of those people who have performed the test and present the risk polymorphisms.

The FEHV clinic is a pioneer in the use of genetic diagnostic tests, being at the forefront of science.

References

Lazo M, Clark JM. The epidemiology of non-alcoholic fatty liver disease: a global perspective. Semin Liver Dis 2008; 28: 339-50.
Romeo S, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40: 1461-5.
Sookoian S. Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011; 53: 1883–9.
Singal AG, et al. The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: a meta-analysis. Am J Gastroenterol. 2014; 109: 325-34.
Liu YL, et al. Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol 2014; 61: 75–81.
Brouwer WP, et al. The impact of PNPLA3 (rs738409 C>G) polymorphisms on liver histology and long-term clinical outcome in chronic hepatitis B patients. Liver Int 2014; doi: 10.1111/liv.12695. [Epub ahead of print].