Open AccessAssociation of MTTP gene variants with pediatric NAFLD: A candidate-gene-based analysis of single nucleotide variations in obese children
Author(s) -
DeZai Dai,
Feiqiu Wen,
Shiwei Zhou,
Zhe Su,
Guosheng Liu,
Mingbang Wang,
Jian Zhou,
Fusheng He
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0185396
Subject(s) - nonalcoholic fatty liver disease , single nucleotide polymorphism , lipid metabolism , biology , medicine , candidate gene , genetics , fatty liver , endocrinology , genotype , gene , bioinformatics , disease
Objective We used targeted next-generation sequencing to investigate whether genetic variants of lipid metabolism-related genes are associated with increased susceptibility to nonalcoholic fatty liver disease (NAFLD) in obese children. Methods A cohort of 100 obese children aged 6 to 18 years were divided into NAFLD and non-NAFLD groups and subjected to hepatic ultrasound, anthropometric, and biochemical analyses. We evaluated the association of genetic variants with NAFLD susceptibility by investigating the single nucleotide polymorphisms in each of 36 lipid-metabolism-related genes. The panel genes were assembled for target region sequencing. Correlations between single nucleotide variations, biochemical markers, and clinical phenotypes were analyzed. Results 97 variants in the 36 target genes per child were uncovered. Twenty-six variants in 16 genes were more prevalent in NAFLD subjects than in in-house controls. The mutation rate of MTTP rs2306986 and SLC6A2 rs3743788 was significantly higher in NAFLD subjects than in non-NAFLD subjects (OR: 3.879; P = 0.004; OR: 6.667, P = 0.005). Logistic regression analysis indicated the MTTP variant rs2306986 was an independent risk factor for NAFLD (OR: 23.468, P = 0.044). Conclusions The results of this study, examining a cohort of obese children, suggest that the genetic variation at MTTP rs2306986 was associated with higher susceptibility to NAFLD. This may contribute to the altered lipid metabolism by disruption of assembly and secretion of lipoprotein, leading to reducing fat export from the involved hepatocytes.