Pediatric Gastroenterology, Hepatology & Nutrition

The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition (대한소아소화기영양학회)
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The PNPLA3 rs738409 Variant but not MBOAT7 rs641738 is a Risk Factor for Nonalcoholic Fatty Liver Disease in Obese U.S. Children of Hispanic Ethnicity

  • Mansoor, Sana (Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nemours/Alfred I. duPont Hospital for Children) ;
  • Maheshwari, Anshu (Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nemours/Alfred I. duPont Hospital for Children) ;
  • Guglielmo, Matthew Di (Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nemours/Alfred I. duPont Hospital for Children) ;
  • Furuya, Katryn (Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nemours/Alfred I. duPont Hospital for Children) ;
  • Wang, Makala (Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children) ;
  • Crowgey, Erin (Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children) ;
  • Molle-Rios, Zarela (Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nemours/Alfred I. duPont Hospital for Children) ;
  • He, Zhaoping (Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children)
  • Received : 2021.03.01
  • Accepted : 2021.07.17
  • Published : 2021.09.15
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Abstract

Purpose: The rs641738 C>T in membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) is implicated, along with the rs738409 C>G polymorphism in patatin-like phospholipase domain-containing protein 3 (PNPLA3), in nonalcoholic fatty liver disease (NAFLD). The association of these polymorphisms and NAFLD are investigated in Hispanic children with obesity. Methods: Obese children with and without NAFLD were enrolled at a pediatric tertiary care health system and genotyped for MBOAT7 rs641738 C>T and PNPLA3 rs738409 C>G. NAFLD was characterized by the ultrasonographic presence of hepatic steatosis along with persistently elevated liver enzymes. Genetic variants and demographic and biochemical data were analyzed for the effects on NAFLD. Results: Among 126 enrolled subjects, 84 in the case group had NAFLD and 42 in the control group did not. The two groups had similar demographic distribution. NAFLD was associated with abnormal liver enzymes and elevated triglycerides and cholesterol (p<0.05). Children with NAFLD had higher percentage of PNPLA3 GG genotype at 70.2% versus 31.0% in non-NAFLD, and lower MBOAT7 TT genotype at 4.8% versus 16.7% in non-NAFLD (p<0.05). PNPLA3 rs738409 C>G had an additive effect in NAFLD; however, MBOAT7 rs641738 C>T had no effects alone or synergistically with PNPLA3 polymorphism. NAFLD risk increased 3.7-fold in subjects carrying PNPLA3 GG genotype and decreased in MBOAT7 TT genotype. Conclusion: In Hispanic children with obesity, PNPLA3 rs738409 C>G polymorphism increased the risk for NAFLD. The role of MBOAT7 rs641738 variant in NAFLD is less evident.

Keywords

Acknowledgement

The authors thank the researchers at the Biomolecular Core Lab and Gastroenterology Research Lab and the Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, for their contribution to this work.

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