Abstract
BACKGROUND: Metabolic disorder-associated fatty liver disease (MAFLD) in children is an emerging global health concern, particularly in terms of obesity and metabolic disturbances. Inflammation plays a crucial role in the pathogenesis of MAFLD, with adenosine deaminase (ADA) and interleukin-1 receptor antagonist (IL-1Ra) being potential contributors. PURPOSE: This study aimed to assess the association between ADA G22A and IL-1RN single nucleotide polymorphisms (SNPs) and MAFLD among a cohort of Egyptian children. It also aimed to evaluate the validity of very low-density lipoprotein (VLDL)/high-density lipoprotein cholesterol (HDL-C) and triglyceride-to-HDL-C ratios for predicting MAFLD in obese children. METHODS: One hundred obese children and 50 healthy controls were included. The obese group was further categorized into those with versus without MAFLD. IL-1Ra and ADA G22A SNPs were evaluated using conventional polymerase chain reaction (PCR) and restriction fragment length polymorphism-PCR, respectively. VLDL/HDL and triglyceride-to-HDL ratios were calculated from the lipid profiles of the included participants. RESULTS: The obese children had significantly higher weight, weight z score, body mass index (BMI), BMI z score, and waist circumference than the healthy controls. These parameters were considerably higher in children with versus without MAFLD P<0.05 all. The GG genotype and G allele of ADA G22A were significantly more frequent in the obese children versus controls (P<0.05 for both); however, no significant difference was observed between obese children with versus without MAFLD. Regarding IL-1RN polymorphisms, the *2/*2 genotype was more common in the controls and obese children without MFLD, whereas the *1/*2 genotype was prevalent in the obese children with MAFLD (P<0.05 all). A VLDL/HDL-C cutoff ratio of >0.6308 showed 80% sensitivity, 58% specificity, a 65.6% positive predictive value (PPV), a 74.4% negative predictive value, and 69% accuracy at differentiating among MAFLD cases. The triglyceride-to-HDL-C ratio cutoff of >3.0685 demonstrated high specificity (88%) and a high PPV (84.2%) but moderate sensitivity (64%) and overall accuracy (76%). CONCLUSION: The current study's findings support the possible genetic role of ADA G22A in childhood obesity, with a significant role for the IL-1RN SNP in the development of MAFLD in obese children. The triglyceride-to-HDL-C ratio was more useful than the VLDL/HDL-C ratio for predicting pediatric MAFLD.