Clinical Indications

Background Information for Non-Alcoholic Fatty Liver Disease Susceptibility (PNPLA3) Genotyping:

Characteristics: Fatty liver disease is the accumulation of excessive triglycerides in the liver that may cause an inflammatory response, which can progress to fibrosis, cirrhosis, and liver cancer. The c.444C>G; p.I148M variant in the PNPLA3 gene confers an increased risk for the onset and progression of non-alcoholic fatty liver disease (NAFLD). This allele also confers an increased risk for the onset and progression of cirrhosis among individuals with alcoholic liver disease.

Incidence: NAFLD occurs in approximately 20-30 percent of individuals in the U.S.

G Allele Frequency: Varies by ethnicity; Latino 0.57, East Asian 0.38, European 0.23, South Asian 0.22, Africans 0.14.

Cause: Risk factors for non-alcoholic fatty liver disease include obesity, diabetes, insulin resistance and genetic risk factors including PNPLA3 c.444C>G; p.I148M.

Inheritance: Multifactorial.

Clinical Sensitivity: Unknown.

Variant Tested: PNPLA3 c.444C>G; p.I148M (rs738409).

Methodology: Polymerase chain reaction (PCR) and fluorescence monitoring.

Analytical Sensitivity and Specificity: Greater than 99 percent.

Limitations: Only the c.444C>G; p.I148M variant in the PNPLA3 gene will be targeted. Diagnostic errors can occur due to rare sequence variations.