A complete linkage disequilibrium in a haplotype of three SNPs in Fat Mass and Obesity associated (FTO) gene was strongly associated with anthropometric indices after controlling for calorie intake and physical activity.

BACKGROUND: The underlying mechanism of the effect of FTO genotype on body mass index (BMI) and body composition is unknown. The objective of the study was to investigate the association of FTO gene polymorphisms with anthropometric indices in adolescent boys after adjustments for dietary intake and physical activity. METHODS: In this school-based study, we enrolled 123 male adolescents without extra weight and 110 male adolescents with body mass index (BMI) higher than + 1 Z-score. The DNA samples were genotyped for the FTO gene polymorphisms by DNA Sequencing. BMI and body composition were assessed using bioelectrical impedance analyzer scale. Association of the FTO polymorphisms with Weight, height, BMI, body fat percent and skeletal muscle percent were investigated. Data on potential confounders (calorie intake and physical activity) were collected through the use of pre-tested questionnaires. RESULTS: Adolescents with higher BMI and body fat percent and lower skeletal muscle percent were more likely to have a newly found haplotype of rs9930506, rs9930501 & rs9932754 (GGT) in the first intron of the FTO with complete linkage disequilibrium (LD) compared with those with the lower BMI (6.15;2.28-16.63), body fat percent (9.54;0.92-47.44) and higher skeletal muscle percent (9.26;1.85-46.38). This association was not changed after controlling for age. Additional adjustments for calorie intake and physical activity did not alter the association. CONCLUSIONS: A haplotype in the first intron of the FTO gene had a strong association with obesity indices in adolescent boys after adjustments for calorie intake and physical activity. It's suggested that the FTO genotype exert its effects on adolescents' anthropometric indices as haplotype and through mechanisms other than changes in calorie intake and expenditure. TRIAL REGISTRATION: This paper reports the first phase of a comprehensive interventional study (Interactions of Genetics, lifestyle and anthropometrics study or IGLA study) and is retrospectively registered in the Iranian Registry of Clinical Trials as IRCT2016020925699N2. Date registered: April 24, 2016. ( http://www.irct.ir/searchresult.php?id=25699&number=2 ).

Up-regulation of FTO gene expression was associated with increase in skeletal muscle mass in overweight male adolescents.

INTRODUCTION: The modifying effect of FTO gene expression level on change in body mass index and body composition has not been studied before. This study aimed to investigate the association between change in the expression level of the FTO gene and changes in anthropometric measurements in obese and overweight adolescent boys. MATERIAL AND METHODS: Eighty-four boys aged 12 to 16 years participated in this longitudinal study. A Bio Impedance Analyzer (BIA) was used to estimate percentage of body fat (%BF) and percentage of skeletal muscle (%SM). The FTO gene expression level in peripheral blood mononuclear cells was assessed using quantitative real-time PCR (qPCR). All measurements were performed at baseline and after 18 weeks. RESULTS: After 18 weeks, mean weight was reduced by 2.39 kg, body mass index by 0.09 kg/m2, %BF by 0.82% and %SM increased by 0.44%. Moreover, the level of FTO gene expression increased 0.42-fold higher than baseline. The change in expression level of the FTO gene was positively associated with change in %SM (ß = 0.31, p = 0.02). CONCLUSIONS: FTO gene expression change was associated with change in %SM in male adolescents. Future studies are required to assess the interactions between FTO gene expression in different tissues and body composition.

A haplotype of three SNPs in FTO had a strong association with body composition and BMI in Iranian male adolescents.

BACKGROUND: Single-nucleotide polymorphisms (SNPs), which are located in the first intron of the FTO gene, are reported to be associated with body weight and the body mass index (BMI). However, their effects on anthropometric measurements in adolescents are poorly understood. OBJECTIVE: This study aimed to investigate the association of three adjacent polymorphisms (rs9930506, rs9930501, & rs9932754) in the FTO gene with anthropometric indices in Iranian adolescent males. DESIGN: The participants comprised a total of 237 adolescent males who were recruited randomly from two high schools in Tehran, Iran. The DNA samples were genotyped for the FTO gene polymorphisms by DNA sequencing. BMI, body fat percentage (BF%), and body muscle percentage (BM%) were determined using a validated bioelectrical impedance analysis scale. The association of the FTO polymorphisms with weight, height, BMI, BF%, and BM% was investigated. RESULTS: A haplotype of rs9930506, rs9930501, and rs9932754 (GGT) in the first intron of the FTO with complete linkage disequilibrium (LD) was found to be significantly associated with higher weight (OR = 1.32), BMI (OR = 5.36) and BF% (OR = 1.46), and lower BM% (OR = 3.59) (all P<0.001). None of the students with GGC genotypes were underweight, while all of the students with AAT genotypes had high muscle mass. CONCLUSIONS: A haplotype in the first intron of the FTO gene had a strong association with obesity indices in Iranian adolescent males. The FTO gene polymorphisms might have greater effects on anthropometric indices than what was previously imagined. Moreover, we suggested that the FTO gene exerted their effects on anthropometric measurements through haplotypes (and not single SNPs).