Chirita-Emandi Adela, Serban Costela Lacrimioara, Paul Corina, Andreescu Nicoleta, Velea Iulian, Mihailescu Alexandra, Serafim Vlad, Tiugan Diana-Andreea, Tutac Paul, Zimbru Cristian, Puiu Maria, Niculescu Mihai Dinu
Department of Microscopic Morphology - Genetics, Center of Genomic Medicine, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania.
Regional Center of Medical Genetics Timis, Clinical Emergency Hospital for Children "Louis Turcanu", Timisoara, Romania.
Diabetes Metab Syndr Obes. 2020 Nov 19;13:4483-4494. doi: 10.2147/DMSO.S277268. eCollection 2020.
Insulin resistance plays a major role in metabolic syndrome and is recognized as the most common risk factor for non-alcoholic fatty liver disease (NAFLD). Identifying predictors for insulin resistance could optimize screening and prevention.
To evaluate the contribution of multiple single nucleotide polymorphisms across genes related to NAFLD and choline metabolism, in predicting insulin resistance in children with obesity.
One hundred fifty-three children with obesity (73 girls), aged 7-18 years, were evaluated within the NutriGen Study (ClinicalTrials.gov-NCT02837367). Insulin resistance was defined by Homeostatic Model Assessment for insulin-resistance cut-offs that accommodated pubertal and gender differences. Anthropometric, metabolic, intake-related variables, and 55 single nucleotide polymorphisms related to NAFLD and choline metabolism were evaluated. Gene-gene interaction effects were assessed using Multiple Data Reduction Software.
Sixty percent (93/153) of participants showed insulin resistance (58.7% of boys, 63% of girls). Children with insulin resistance presented significantly higher values for standardized body mass index, triglycerides, transaminases and plasma choline when compared to those without insulin resistance. Out of 52 single nucleotide polymorphisms analysed, the interaction between genotypes (rs12676) and (rs738409) predicted insulin resistance. The model presented a 6/10 cross-validation consistency and 0.58 testing accuracy. Plasma choline levels and alanine aminotransferase modulated the gene interaction effect, significantly improving the model.
The interaction between genotypes in and genes, modulated by choline and alanine aminotransferase levels, predicted insulin-resistance status in children with obesity. If replicated in larger cohorts, these findings could help identify metabolic risk in children with obesity.
胰岛素抵抗在代谢综合征中起主要作用，并且被认为是非酒精性脂肪性肝病（NAFLD）最常见的危险因素。识别胰岛素抵抗的预测指标可以优化筛查和预防措施。
评估与NAFLD和胆碱代谢相关基因中的多个单核苷酸多态性对肥胖儿童胰岛素抵抗的预测作用。
在营养基因组研究（ClinicalTrials.gov - NCT02837367）中对153名7至18岁的肥胖儿童（73名女孩）进行了评估。胰岛素抵抗通过考虑青春期和性别差异的胰岛素抵抗稳态模型评估临界值来定义。评估了人体测量学、代谢、与摄入量相关的变量以及与NAFLD和胆碱代谢相关的55个单核苷酸多态性。使用多重数据约简软件评估基因 - 基因相互作用效应。
60%（93/153）的参与者表现出胰岛素抵抗（男孩为58.7%，女孩为63%）。与无胰岛素抵抗的儿童相比，有胰岛素抵抗的儿童在标准化体重指数、甘油三酯、转氨酶和血浆胆碱方面的值显著更高。在分析的52个单核苷酸多态性中，基因型（rs12676）和（rs738409）之间的相互作用可预测胰岛素抵抗。该模型呈现出6/10的交叉验证一致性和0.58的测试准确性。血浆胆碱水平和丙氨酸转氨酶调节了基因相互作用效应，显著改善了模型。
由胆碱和丙氨酸转氨酶水平调节的 基因和 基因中的基因型相互作用可预测肥胖儿童的胰岛素抵抗状态。如果在更大的队列中得到验证，这些发现可能有助于识别肥胖儿童的代谢风险。
