Mitochondrial TRNA Variants In Chinese Children With Obesity

Objective:Childhood obesity is one of the most important chronic worldwide diseases and becoming a major public health problem in the 21st century.Many factors including diet,life style,genetic and epigenetic changes contribute to obesity.The Mitochondrial dysfunction plays an important role in the development of obesity.Abnormal mitochondrial function causes imbalance of energy metabolism,which will lead to obesity.tRNA is a key effector in mitochondrial biological processes.Mitochondrial tRNA gene mutations is an important cause of mitochondrial dysfunction.Therefore,tRNA mutations may disturb mitochondrial function and energy metabolism,which ultimately lead to obesity.Our study aims to explore the relationship between mitochondrial tRNA gene and obesity in Chinese obese children.Methods:(1)Sample collection:according to the obesity diagnostic criteria,blood samples of 65 obese children and 376 children with normal controls who met the inclusion criteria were collected and comprehensive systematic clinical examination was performed.(2)Mitochondrial gene extraction and sequencing:DNA extraction,PCR amplification,mitochondrial gene sequencing of the above samples using next-generation sequencing technology.(3)Screen candidate mitochondrial tRNA mutation sites with secondary structure,conservation analysis,mitochondrial haplogroup analysis,family analysis,etc.(4)Analysis of clinical data of obese children.Results:The results showed that a total of 4 putative mitochondrial tRNA mutations met the following criteria:frequency of gene mutation<0.001,CI value>75%,possible functional or structural changes in the control group.These mutations were tRNAArgA10461G,tRNACysT5802C,tRNAThrG15894A,tRNAGlyA10029G,which were considered to be associated with childhood obesity.In addition,the haplogroup analysis showed that haplogroups A,D,G,M7,M8,M10,Y and R were higher in Chinese obese children than in normal controls.After statistical analysis,M7 and R were positively associated with obesity(M7:OR 2.448,95%CI 1.19-5.354,P 0.025;R:OR 4.393,95%CI 1.35-14.291,P 0.014).Haplogroup F is negatively correlated with obesity(F:OR 0.167,95%CI 0.04-0.702,P 0.015).Conclusion:In summary,this study found a close correlation between mitochondrial tRNA genes and obesity.This means that maternal obesity is an important susceptibility factor for childhood obesity.These functional sites require further functional analysis.Moreover,the haplogroup M7 and R may be more inclined to obesity in the Chinese population,while mitochondrial haplogroup F may confer resistance against obesity.This study provides a new perspective for better understanding the mechanism of obesity and a reference for controlling childhood obesity.