title: Non-alcoholic fatty liver disease and subclinical atherosclerosis: A comparison of metabolically- versus genetically-driven excess fat hepatic storage.
abstract: Non-alcoholic fatty liver disease (NAFLD) is frequently associated with atherosclerosis. However, it is unclear whether this association is related to excess fat liver storage per se or to metabolic abnormalities that typically accompany NAFLD. To investigate this, we compared individuals with hepatic steatosis driven by metabolic disturbances to those with hepatic steatosis associated with the rs738409 GG genotype in the patatin-like phospholipase domain-containing 3 gene (PNPLA3).
  
  
  
  Carotid intima-media thickness (CIMT), as a surrogate marker of subclinical atherosclerosis, was measured in 83 blood donors with the mutant GG genotype (group G), 100 patients with features of metabolic syndrome (MetS) but the wildtype CC genotype (group M), and 74 blood donors with the wildtype CC genotype (controls). Fatty liver was evaluated by ultrasonography and hepatic fat fraction (HFF) was measured using magnetic resonance (MRS/MRI) in 157 subjects.
  
  
  
  Compared with group G and controls, group M subjects were older and had increased adiposity indices, dyslipidemia, insulin resistance and elevated transaminase levels (all p < 0.05). They also had a more fatty liver on both ultrasonography and MRS/MRI. After adjustment for confounders (including severity of hepatic steatosis), the median CIMT in group M (0.84 [0.70-0.95] mm) was significantly greater than that in group G (0.66 [0.55-0.74] mm; p < 0.001), which was similar to that in controls (0.70 [0.64-0.81] mm). Results were similar in the subgroup evaluated using MRS/MRI.
  
  
  
  Excess liver fat accumulation appeared to increase the burden of subclinical atherosclerosis only when it is associated with metabolic abnormalities.
authors.affiliation: Departments of Internal Medicine and Medical Specialties, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy. Electronic address: alessia.dicostanzo@uniroma1.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Di Costanzo
authors.affiliation: Departments of Internal Medicine and Medical Specialties, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: D'Erasmo
authors.affiliation: Departments of Internal Medicine and Medical Specialties, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Licia
authors.initials: L
authors.lastname: Polimeni
authors.affiliation: Departments of Internal Medicine and Medical Specialties, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy; Department of Anatomical, Histological, Forensic Medicine and Orthopedics, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Baratta
authors.affiliation: Departments of Internal Medicine and Medical Specialties, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Coletta
authors.affiliation: Radiological Sciences Department, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Di Martino
authors.affiliation: Departments of Internal Medicine and Medical Specialties, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Loffredo
authors.affiliation: Departments of Internal Medicine and Medical Specialties, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Perri
authors.affiliation: Department of Cellular Biotechnologies and Hematology, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ceci
authors.affiliation: Departments of Internal Medicine and Medical Specialties, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Montali
authors.affiliation: Immunohematology and Transfusion Medicine Unit, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Girelli
authors.affiliation: Immunohematology and Transfusion Medicine Unit, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: De Masi
authors.affiliation: Department of Molecular Medicine, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Angeloni
authors.affiliation: Radiological Sciences Department, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Catalano
authors.affiliation: Departments of Internal Medicine and Medical Specialties, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Maranghi
authors.affiliation: Departments of Internal Medicine and Medical Specialties, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Ben
authors.affiliation: Department of Public Health and Infectious Disease, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelico
authors.affiliation: Departments of Internal Medicine and Medical Specialties, "La Sapienza" University, Policlinico Umberto I Hospital, Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Arca
mesh_terms: D000328:Adult; D058070:Asymptomatic Diseases; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000209:etiology*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008049:Lipase / Q000235:genetics*; D050356:Lipid Metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D014463:Ultrasonography; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: Atherosclerosis; Carotid intima-media thickness; Ectopic fat storage; Non-alcoholic fatty liver disease; PNPLA3