title: Association of the I148M/PNPLA3 variant with elevated alanine transaminase levels in normal-weight and overweight/obese Mexican children.
abstract: OBJECTIVE
  Non-alcoholic fatty liver disease (NAFLD) and elevated alanine transaminase (ALT) levels are common in obese Hispanic adults and children. Recently, a PNPLA3 gene variant (I148M) was strongly associated with NAFLD and higher ALT levels in obese adults, including Hispanics. The aims of this study were to estimate the frequency of elevated ALT levels, and to address the influence of obesity and PNPLA3/I148M on ALT levels in a general population sample of Mexican school-aged children.
  
  
  METHODS
  A total of 1037 non-related Mexican children aged 6 to 12 years were genotyped for the I148M variant. Anthropometric, clinical and metabolic parameters were collected from all participants.
  
  
  RESULTS
  Elevated ALT levels (>35 U/L) were more frequent in obese (26.9%) and overweight (9.3%) than in normal weight children (2.2%). The M148M genotype was significantly associated with elevated ALT levels in this population (OR=3.7, 95% CI 2.3-5.9; P=3.7×10(-8)), and children carrying the M148M genotype showed significantly lower HDL cholesterol levels and BMI z-core (P=0.036 and 0.015, respectively). On stratifying by BMI percentile, this genotype conferred a much greater risk of elevated ALT levels in normal weight (OR=19.9, 95% CI 2.5-157.7; P=0.005) than overweight and obese children (OR=3.4, 95% CI 1.3-8.9; P=0.014 and OR=3.1, 95% CI 1.7-5.5; P=1.4 x10(-4), respectively).
  
  
  CONCLUSIONS
  The I148M PNPLA3 variant is strongly associated with elevated ALT levels in normal weight and overweight/obese Mexican children. Thus, the M148M genotype may be considered as an important risk factor for liver damage in this population.
authors.affiliation: Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, Mexico.
authors.forename: Elena
authors.initials: E
authors.lastname: Larrieta-Carrasco
authors.forename: Paola
authors.initials: P
authors.lastname: León-Mimila
authors.forename: Teresa
authors.initials: T
authors.lastname: Villarreal-Molina
authors.forename: Hugo
authors.initials: H
authors.lastname: Villamil-Ramírez
authors.forename: Sandra
authors.initials: S
authors.lastname: Romero-Hidalgo
authors.forename: Leonor
authors.initials: L
authors.lastname: Jacobo-Albavera
authors.forename: Roxana
authors.initials: R
authors.lastname: Gutiérrez-Vidal
authors.forename: Blanca E
authors.initials: BE
authors.lastname: López-Contreras
authors.forename: Luz E
authors.initials: LE
authors.lastname: Guillén-Pineda
authors.forename: Fausto
authors.initials: F
authors.lastname: Sánchez-Muñoz
authors.forename: Rafael
authors.initials: R
authors.lastname: Bojalil
authors.forename: Ana M
authors.initials: AM
authors.lastname: Mejía-Domínguez
authors.forename: Nahúm
authors.initials: N
authors.lastname: Méndez-Sánchez
authors.forename: Aaron
authors.initials: A
authors.lastname: Domínguez-López
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Aguilar-Salinas
authors.forename: Samuel
authors.initials: S
authors.lastname: Canizales-Quinteros
mesh_terms: D017668:Age of Onset; D000410:Alanine Transaminase / Q000032:analysis / Q000097:blood*; D019943:Amino Acid Substitution / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D056865:Ideal Body Weight / Q000235:genetics / Q000502:physiology; D007532:Isoleucine / Q000235:genetics; D008049:Lipase / Q000235:genetics*; D008107:Liver Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008715:Methionine / Q000235:genetics; D008800:Mexico / Q000453:epidemiology; D009765:Obesity / Q000097:blood / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D050177:Overweight / Q000097:blood / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000410:Alanine Transaminase; D007532:Isoleucine; D008049:Lipase; D008565:Membrane Proteins; D008715:Methionine; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent