title: Isoleucine-to-methionine substitution at residue 148 variant of PNPLA3 gene and metabolic outcomes in gestational diabetes.
abstract: BACKGROUND
  A single nucleotide polymorphism (SNP) of the patatin-like phospholipase-3 (PNPLA3)/adiponutrin gene (rs738409 C>G) is strongly associated with nonalcoholic fatty liver disease; to our knowledge, no data are available on the impact of this PNPLA3 SNP on liver and metabolic outcomes during pregnancy in patients with gestational diabetes (GD).
  
  
  OBJECTIVE
  We evaluated the impact of the PNPLA3 rs738409 SNP on liver enzymes, metabolic indexes, and maternal and neonatal outcomes in 200 GD patients enrolled in a lifestyle intervention.
  
  
  METHODS
  In a randomized trial with a 2 × 2 factorial design, exercise significantly improved maternal and neonatal outcomes in GD patients. Effects of the G allele on metabolic and liver indexes and maternal and neonatal outcomes were evaluated in these patients.
  
  
  RESULTS
  At the end of the trial, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly lower and liver enzymes significantly higher in PNPLA3 G-allele carriers. In a multiple regression model, the G allele was associated directly with aspartate aminotransferase (β = 2.60; 95% CI: 0.99, 4.20), alanine aminotransferase (β = 3.70; 95% CI: 1.78, 5.62), and γ-glutamyl transferase (β = 3.70; 95% CI: 0.80, 6.60) and inversely with insulin (β = -2.01; 95% CI: -3.24, -0.78) and HOMA-IR (β = -0.39; -0.64, -0.14) values at the end of the trial. In a multiple logistic regression model, the G allele was associated directly with risk of developing liver enzyme elevation during pregnancy (OR: 4.21; 95% CI: 1.78, 9.97) and inversely with the birth of large-for-gestational-age newborns (OR: 0.19; 95% CI: 0.06, 0.62). No diet × genotype or exercise × genotype interaction was shown.
  
  
  CONCLUSIONS
  The PNPLA3 SNP rs738409 G allele was associated with risk of mildly elevated transaminases in GD independent of a lifestyle intervention and despite a significant reduction in insulin resistance and risk of macrosomic offspring. This trial was registered at clinicaltrials.gov as NCT01506310.
authors: From the Departments of Medical Sciences (SB, RG, SC, VP, SP, MD, EG, and MC) and Surgical Sciences (G Menato), University of Turin, Turin, Italy, and the Gradenigo Hospital, Turin, Italy (G Musso).
authors: Simona
authors: S
authors: Bo
authors: From the Departments of Medical Sciences (SB, RG, SC, VP, SP, MD, EG, and MC) and Surgical Sciences (G Menato), University of Turin, Turin, Italy, and the Gradenigo Hospital, Turin, Italy (G Musso).
authors: Roberto
authors: R
authors: Gambino
authors: From the Departments of Medical Sciences (SB, RG, SC, VP, SP, MD, EG, and MC) and Surgical Sciences (G Menato), University of Turin, Turin, Italy, and the Gradenigo Hospital, Turin, Italy (G Musso).
authors: Guido
authors: G
authors: Menato
authors: From the Departments of Medical Sciences (SB, RG, SC, VP, SP, MD, EG, and MC) and Surgical Sciences (G Menato), University of Turin, Turin, Italy, and the Gradenigo Hospital, Turin, Italy (G Musso).
authors: Stefania
authors: S
authors: Canil
authors: From the Departments of Medical Sciences (SB, RG, SC, VP, SP, MD, EG, and MC) and Surgical Sciences (G Menato), University of Turin, Turin, Italy, and the Gradenigo Hospital, Turin, Italy (G Musso).
authors: Valentina
authors: V
authors: Ponzo
authors: From the Departments of Medical Sciences (SB, RG, SC, VP, SP, MD, EG, and MC) and Surgical Sciences (G Menato), University of Turin, Turin, Italy, and the Gradenigo Hospital, Turin, Italy (G Musso).
authors: Silvia
authors: S
authors: Pinach
authors: From the Departments of Medical Sciences (SB, RG, SC, VP, SP, MD, EG, and MC) and Surgical Sciences (G Menato), University of Turin, Turin, Italy, and the Gradenigo Hospital, Turin, Italy (G Musso).
authors: Marilena
authors: M
authors: Durazzo
authors: From the Departments of Medical Sciences (SB, RG, SC, VP, SP, MD, EG, and MC) and Surgical Sciences (G Menato), University of Turin, Turin, Italy, and the Gradenigo Hospital, Turin, Italy (G Musso).
authors: Ezio
authors: E
authors: Ghigo
authors: From the Departments of Medical Sciences (SB, RG, SC, VP, SP, MD, EG, and MC) and Surgical Sciences (G Menato), University of Turin, Turin, Italy, and the Gradenigo Hospital, Turin, Italy (G Musso).
authors: Maurizio
authors: M
authors: Cassader
authors: From the Departments of Medical Sciences (SB, RG, SC, VP, SP, MD, EG, and MC) and Surgical Sciences (G Menato), University of Turin, Turin, Italy, and the Gradenigo Hospital, Turin, Italy (G Musso).
authors: Giovanni
authors: G
authors: Musso
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D001219:Aspartate Aminotransferases / Q000097:blood; D016640:Diabetes, Gestational / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D002149:Energy Intake; D015444:Exercise; D005260:Female; D015438:Health Behavior; D006801:Humans; D007328:Insulin / Q000097:blood; D007532:Isoleucine / Q000737:chemistry*; D008019:Life Style; D016014:Linear Models; D008049:Lipase / Q000737:chemistry / Q000235:genetics*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008715:Methionine / Q000737:chemistry*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000235:genetics; D011795:Surveys and Questionnaires; D055815:Young Adult; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D007328:Insulin; D007532:Isoleucine; D008049:Lipase; D008565:Membrane Proteins; D008715:Methionine; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: ALT; GDM; NAFLD; PNPLA3; fatty liver; liver enzymes; transaminase; trial