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Key Highlights
- Common genetic variants in one-carbon and lipid metabolic pathways can interfere with nutrient metabolism and lipid synthesis, increasing the risk of NAFLD and its complications.
- Although NAFLD is the leading cause of chronic liver disease and affects an estimated 290 million people worldwide, no FDA-approved medications currently exist to treat it.
- Using genetic tests to identify individuals at heightened risk of developing NAFLD and related complications is an effective and viable method of improving the prognosis for NAFLD patients through targeted diet modification and lifestyle changes.
- Providing genetic testing and education can empower patients to take charge of their health with a personalized nutrition treatment plan that is specific to their DNA. This is the future of individualized healthcare.
Introduction
Nonalcoholic fatty liver disease (NAFLD) has become increasingly prevalent worldwide in the past decade, with an estimated 1 in 3 Americans currently affected by the disease.1 Because most people with NAFLD are unaware that they have it, disease progression and complications can become severe before treatment is initiated. A subset of NAFLD, nonalcoholic steatohepatitis (NASH), includes the presence of inflammation and liver damage along with fatty liver. Studies indicate that roughly 25% of patients with NAFLD will go on to develop NASH, increasing their chances of developing cirrhosis and fibrosis.
There are currently no FDA-approved treatments for NAFLD, although several experimental drug models are in development. Current treatment approaches include weight loss and diet modifications to decrease inflammation, fat accumulation, and fibrosis in the liver.
While multiple nutrients have been implicated in the development and prevention of a wide range of disease states, genetic variations can impact the efficiency of nutrient metabolism, thereby changing nutritional requirements from person to person. This is especially true in the case of NAFLD, which is directly affected by de novo lipid synthesis as well as the type and amount of fat, fiber, and micronutrients in the diet. Because people do not metabolize each of these nutrients in the same way or to the same extent due to genetic differences, employing tests to identify aberrations in NAFLD-related genes and applying precision nutrition treatments to the nutrient pathways affected is a sophisticated yet simple way to improve patient outcomes and lower the risk of future complications from NAFLD.
In response to an unmet need for improved diagnosis and treatment of NAFLD, SNP Therapeutics has developed a genetic test and targeted nutrition approach to identify potential NAFLD patients and their risk of developing the disease if no dietary or lifestyle changes are made. Using each patient’s test results, an individualized nutrition care plan can be implemented to prevent the development or progression of this potentially fatal disease.
Risk Factors and Genetic Variants in the Development of NAFLD
Risk factors for NAFLD include obesity, type 2 diabetes, and metabolic syndrome. While NAFLD affects an estimated 30% of the U.S. population, it is prevalent in over 90% of individuals who are obese. In a 2014 study of 348 Korean patients, those with NAFLD had central obesity scores 5.6 times higher and fasting glucose levels three times higher than controls. They also displayed abnormal blood cholesterol and triglyceride levels.2 Central obesity, hypertension, elevated blood glucose, cholesterol, and triglycerides are all hallmarks of metabolic syndrome.
Patients with both NAFLD and metabolic syndrome are also at increased risk of hepatocellular carcinoma (HCC). In addition, obesity, metabolic syndrome, and steatosis are often seen together, although studies have not determined a cause-and-effect relationship between the three conditions.
A landmark study published in 2013 demonstrated the importance of identifying genetic signatures by examining SNP clusters (rather than single polymorphisms) in genes that affect one-carbon nutrient metabolism and hepatic lipid packaging and transport. Patients who developed steatosis after consuming a choline-deficient diet shared common patterns of genetic misspellings, and the severity of steatosis could be predicted by each person’s genetic signature.3 This was an exciting step in establishing the fundamental nature of algorithmic genetic testing to identify SNP signatures for more accurate identification of high-risk patients, as opposed to looking only at single genes.
In the United States, NAFLD is more prevalent among Hispanics than other ethnic groups. This population also has a greater incidence of single nucleotide polymorphisms (SNPs) in the PNPLA3 gene, which is linked to higher rates of steatosis, steatohepatitis, and fibrosis in NAFLD patients.4,5 Thus, Hispanic people as a whole, but particularly those with one or more PNPLA3 SNPs, are at increased risk of morbidity and mortality due to NAFLD. Research has also shown that multiple SNPs in closely related one-carbon nutrient metabolic pathways are highly correlated with the incidence and severity of steatosis in NAFLD patients, regardless of ethnicity.6 Individuals with these genetic variants can be identified pre-diagnosis or early in the disease process through SNP Therapeutics’ genetic test, allowing practitioners to implement potentially life-saving nutrition treatments that are tailored to each patient’s genetic profile.
Other studies have demonstrated that genetic disruptions in the SREBP family of transcription factors, which regulate genes responsible for de novo lipid synthesis, affect rates of hepatic fatty acid and cholesterol synthesis and fat accumulation in the liver. Multiple genetic variants have also been shown to increase insulin resistance and inflammation in addition to de novo lipogenesis, each of which is a risk factor for NAFLD and steatohepatitis. Not surprisingly, suppression of genes active in triglyceride synthesis improves steatohepatitis, blood glucose, and cholesterol levels, while increased activation of the same genes results in elevated liver fatty acid and triglyceride levels.7
SNP Therapeutics’ test has a high rate of accuracy in predicting which at-risk individuals with poor diet habits will go on to develop NAFLD. By making diet changes and managing their weight before a diagnosis of NAFLD is made, these patients may avoid the disease altogether. With patients across the country taking part in genetic testing and nutrition counseling to prevent a NAFLD diagnosis, the quality of life for thousands of patients could be improved, and the burden on our country’s healthcare system significantly lessened.
The Role of Nutrition in NAFLD
Nutritional status, diet composition, and body weight are intimately associated with the development or prevention of NAFLD as well as its treatment. Studies have previously established that diets high in total fat, saturated fat, and trans fat increase the risk of NAFLD development. In contrast, intake of polyunsaturated fats (PUFA) and omega-3 fatty acids lower the risk of NAFLD by improving insulin resistance, blood lipid profiles, and total cholesterol and inhibiting inflammation and fat accumulation in the liver.8
The 2014 study cited above also shows that specific micronutrients play a role in NAFLD. Patients with NAFLD had significantly lower intakes of vitamins A, E, and K, as well as folic acid and sodium. Intake levels of vitamins C and K were negatively associated with NAFLD incidence. In addition, NAFLD patients consumed fewer vegetables, eggs, nuts, seeds, and PUFA-rich foods than those without the condition.9
Other studies have also found diet differences between NAFLD and healthy subjects, with NAFLD patients consuming fewer vegetables, fiber, PUFA, and vitamins A and C. Supplementation with vitamins E and C are effective in improving fibrosis in patients with NASH.10
Choline and other one-carbon nutrients such as betaine are critical for lipid homeostasis in the liver due to the role they play in the transport of very low-density lipoprotein (VLDL) from the liver into the bloodstream. SNPs that impair the conversion of choline and/or betaine to phosphatidylcholine decrease hepatic VLDL output, causing triglycerides to build up in the liver and eventually resulting in steatosis. This has been demonstrated in clinical studies showing that subjects consuming a diet or receiving a parenteral solution deficient in choline develop fatty liver. In addition, those with SNPs affecting choline and other one-carbon metabolic pathways were at higher risk of fatty liver when consuming low levels of dietary choline. Research also indicates that choline and other one-carbon nutrients are involved in pathways related to energy metabolism, thereby making them important players in the development of obesity.11
SNP Therapeutics Genetic Test for NAFLD Diagnosis and Treatment
SNP Therapeutics has developed a genetic test and a medical nutrition treatment approach for individuals with NAFLD that can reduce the risk of disease progression for a significant subset of patients. The test has a 92% accuracy rate in predicting the likelihood that individuals with specific genetic variants, known as their genetic signature, will develop NAFLD if no diet or weight management therapies are implemented.
By examining multiple genes within interrelated pathways that each play a part in the development of a given disease rather than focusing only on single genes, SNP Therapeutics has developed a powerful and accurate method for identifying patients at high risk of NAFLD and steatosis.
A significant number of NAFLD cases can be prevented by identifying genetic variants before clinical signs develop and initiating medical nutrition and lifestyle changes targeted to the nutrient pathways that are affected by each patient’s genetic signature. In patients who have already been diagnosed with NAFLD, a gene-guided nutrition treatment plan can stop or reverse disease progression.
Considerations for Practice
Partnering with SNP Therapeutics to provide an effective, precise genetic test for your patients at risk of or already diagnosed with NAFLD allows you to give individualized care in a way that has not been possible until now. The SNP Therapeutics test is based on a machine learning/AI platform that employs an algorithmic approach to provide practitioners with a comprehensive report detailing each patient’s genetic signature and nutrition treatment plan targeted to their specific SNPs.
By identifying related blockages in metabolic pathways and addressing each patient’s needs based on their genetic test results, healthcare providers can vastly improve outcomes for their patients with NAFLD, stopping the progression of this disease and potentially reversing its course.
Gene-guided nutrition is the future of individualized healthcare. By tailoring nutrition treatment plans to each patient’s genetic signature, health outcomes could look very different for the next generation.
Interested in learning more about this SNP Therapeutics Inc. Program?