Author/Authors :
Vespasiani-Gentilucci, Umberto Internal Medicine - Geriatrics and Hepatology Unit - University Campus Bio-Medico, Rome, Italy , Dell’Unto, Chiara Internal Medicine - Geriatrics and Hepatology Unit - University Campus Bio-Medico, Rome, Italy , Vincentis Antonio De Internal Medicine - Geriatrics and Hepatology Unit - University Campus Bio-Medico, Rome, Italy , Baiocchini, Andrea Laboratory of Pathology of the National Institute for Infectious Diseases - Lazzaro Spallanzani, Rome, Italy , Monache, Marco Delle Hepatology Outpatient Clinic - Colleferro Hospital, Rome, Italy , Cecere, Roberto Hepatology Outpatient Clinic - Colleferro Hospital, Rome, Italy , Maria Pellicelli, Adriano Liver Disease Unit - San Camillo-Forlanini Hospital, Rome, Italy , Giannelli, Valerio Liver Disease Unit - San Camillo-Forlanini Hospital, Rome, Italy , Carotti, Simone Laboratory of Microscopic and Ultrastructural Anatomy - CIR - University Campus Bio-Medico, Rome, Italy , Galati, Giovanni Laboratory of Pathology of the National Institute for Infectious Diseases - Lazzaro Spallanzani, Rome, Italy , Gallo, Paolo Laboratory of Pathology of the National Institute for Infectious Diseases - Lazzaro Spallanzani, Rome, Italy , Valentini, Francesco Internal Medicine - Geriatrics and Hepatology Unit - University Campus Bio-Medico, Rome, Italy , Nonno, Franca Del Laboratory of Pathology of the National Institute for Infectious Diseases - Lazzaro Spallanzani, Rome, Italy , Rosati, Davide University La Sapienza of Rome, Rome, Italy , Morini, Sergio Laboratory of Microscopic and Ultrastructural Anatomy - CIR - University Campus Bio-Medico, Rome, Italy , Antonelli-Incalzi, Raffaele Internal Medicine - Geriatrics and Hepatology Unit - University Campus Bio-Medico, Rome, Italy , Picardi, Antonio Internal Medicine - Geriatrics and Hepatology Unit - University Campus Bio-Medico, Rome, Italy
Abstract :
Background & Aims
Identifying NAFLD patients at risk of progression is crucial to orient medical care and resources. We aimed to verify if the effects determined by different single nucleotide polymorphisms (SNPs) could add up to multiply the risk of NAFLD and NASH-cirrhosis.
Methods
Three study populations, that is, patients diagnosed with NASH-cirrhosis or with noncirrhotic NAFLD and healthy controls, were enrolled. PNPLA3 rs738409, TM6SF2 rs58542926, KLF6 rs3750861, SOD2 rs4880, and LPIN1 rs13412852 were genotyped.
Results
One hundred and seven NASH-cirrhotics, 93 noncirrhotic NAFLD, and 90 controls were enrolled. At least one difference in allele frequency between groups was significant, or nearly significant, for the PNPLA3, TM6SF2, and KLF6 variants (p < 0.001, p < 0.05, and p = 0.06, resp.), and a risk score based on these SNPs was generated. No differences were observed for SOD2 and LPIN1 SNPs. When compared to a score of 0, a score of 1-2 quadrupled, and a score of 3-4 increased 20-fold the risk of noncirrhotic NAFLD; a score of 3-4 quadrupled the risk of NASH-cirrhosis.
Conclusions
The effects determined by disease-associated variants at different loci can add up to multiply the risk of NAFLD and NASH-cirrhosis. Combining different disease-associated variants may represent the way for genetics to keep strength in NAFLD diagnostics.
