Changes in FTO and IRX3 gene expression in obese and overweight male adolescents undergoing an intensive lifestyle intervention and the role of FTO genotype in this interaction.
BACKGROUND
Lifestyle intervention may have a critical effect on the association between genetics and obesity. This study aimed to investigate changes in FTO and IRX3 gene expression in obese and overweight male adolescents undergoing a lifestyle intervention and the role of FTO genotype in this interaction.


METHODS
This study was a field trial of 62 adolescents from boys' high schools in Tehran, Iran. Two schools were randomly allocated as the intervention (n = 30) and control (n = 32) schools. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in peripheral blood mononuclear cells (PBMCs). Anthropometric measurements were assessed at baseline and after 18 weeks of intensive lifestyle intervention.


RESULTS
Our results showed that IRX3 expression in the intervention group was significantly up-regulated compared to baseline (P = 0.007) and compared to the control group (P = 0.011).The intervention group had significantly up-regulated transcripts of IRX3 only in rs9930506 risk allele carriers of the intervention group compared to risk allele carriers of the control group (P = 0.017). Moreover, our data showed that the FTO expression was up-regulated in AA genotype carriers and down-regulated in AG/GG genotype carriers (P = 0.017).


CONCLUSION
Lifestyle modification may exert its effects on obesity through changes in the expression level of the FTO and IRX3 genes. However, FTO genotype plays a role in the extent of the effect of lifestyle changes on gene expression. Further studies are crucial to have a better understanding of the interaction between lifestyle, genetics and anthropometric measurements. Trial registration This paper reports a comprehensive intervention study (Interactions of Genetics, Lifestyle and Anthropometrics study or IGLA study), which is retrospectively registered in the Iranian Registry of Clinical Trials as IRCT2016020925699N2. Date registered: April 24, 2016. ( https://www.irct.ir/searchresult.php?id=25699&number=2 ).
['Doaei|Saeid|S|', 'Kalantari|Naser|N|', 'Izadi|Pantea|P|', 'Salonurmi|Tuire|T|', 'Mosavi Jarrahi|Alireza|A|', 'Rafieifar|Shahram|S|', 'Azizi Tabesh|Ghasem|G|', 'Rahimzadeh|Ghazaleh|G|', 'Gholamalizadeh|Maryam|M|', 'Goodarzi|Mark O|MO|']
D000293:Adolescent D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO D015992:Body Mass Index D001835:Body Weight D002648:Child D015870:Gene Expression D059647:Gene-Environment Interaction D020022:Genetic Predisposition to Disease D005838:Genotype D018398:Homeodomain Proteins D006801:Humans D007492:Iran D008019:Life Style D008297:Male D050177:Overweight D063766:Pediatric Obesity D020641:Polymorphism, Single Nucleotide D040242:Risk Reduction Behavior D013334:Students D014157:Transcription Factors D061217:Weight Reduction Programs
FTO IRX3 Gene expression Obesity Genotype