ORIGINAL RESEARCH
Effects of PNPLA3, TM6SF2 and SAMM50 on the development and severity of non-alcoholic fatty liver disease in children
Kyung Jae Lee,
Jin Soo Moon,
Nan Young Kim,
Jae Sung Ko,
Kyung Jae Lee
Department of Pediatrics, Hallym University College of Medicine, Chuncheon, South Korea
Search for more papers by this authorJin Soo Moon
Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea
Search for more papers by this authorNan Young Kim
Hallym Institute of Translational Genomics & Bioinformatics, Hallym University Medical Center, Anyang, Republic of Korea
Search for more papers by this authorCorresponding Author
Jae Sung Ko
Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea
Correspondence
Jae Sung Ko, Department of Pediatrics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, South Korea.
Email: [email protected]
Search for more papers by this authorKyung Jae Lee,
Jin Soo Moon,
Nan Young Kim,
Jae Sung Ko,
Kyung Jae Lee
Department of Pediatrics, Hallym University College of Medicine, Chuncheon, South Korea
Search for more papers by this authorJin Soo Moon
Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea
Search for more papers by this authorNan Young Kim
Hallym Institute of Translational Genomics & Bioinformatics, Hallym University Medical Center, Anyang, Republic of Korea
Search for more papers by this authorCorresponding Author
Jae Sung Ko
Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea
Correspondence
Jae Sung Ko, Department of Pediatrics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, South Korea.
Email: [email protected]
Search for more papers by this authorSummary
Background
Although genetic variants of PNPLA3, TM6SF2 and SAMM50 have been reported to increase the risk of non-alcoholic fatty liver disease (NAFLD), no pediatric studies have evaluated the association between SAMM50 and NAFLD.
Objective
This study aimed to investigate the risk factors, including genetic variants, of pediatric NAFLD.
Methods
NAFLD was defined as the presence of hepatic steatosis on ultrasound. We included 228 patients with NAFLD (body mass index-Z [BMI-Z] = 2.51 ± 1.01) and 225 controls (BMI-Z = 0.22 ± 1.48). We genotyped four variants of PNPLA3 (rs738409), TM6SF2 (rs58542926) and SAMM50 (rs2073080 and rs3761472) by TaqMan allelic discrimination. The pediatric NAFLD fibrosis score, aspartate transaminase (AST)/platelet ratio index and fibrosis-4 score were used to evaluate the degree of fibrosis. We calculated the genetic risk score for additive effects according to the sum of risk alleles.
Results
The mean age was 12.6 ± 3.5 years. The four genetic variants, male sex and BMI-Z, independently increased susceptibility to NAFLD. These four variants, in addition to fasting insulin and triglycerides, remained significant risk factors with higher odds ratios in children with overweight. These variants increased the alanine aminotransferase (ALT) level and three fibrosis scores independently. As the genetic risk score increased, AST, ALT and the fibrosis scores increased independently.
Conclusion
PNPLA3, TM6SF2 and SAMM50 are associated with the development and severity of pediatric NAFLD. The impact of genetic variants is greater in children with overweight. The four genetic variants have synergetic effects on the severity of pediatric NAFLD.
CONFLICT OF INTEREST
The authors declare no conflicts of interest.
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