rs17817449

This neuroimaging study examined differences in brain structure and function in 93 children (ages 5-10) without obesity, stratified by FTO rs1421085 genotype. Homozygous C allele carriers (CC, n=15) showed significantly greater grey matter volume in the cerebellum and temporal fusiform gyrus (p=0.017-0.050), increased bilateral cerebellar white matter fibre density and cross-section (peak t=6.34, p FWE=0.037), and increased resting-state functional connectivity between the cerebellum and frontotemporal cortices compared to homozygous T allele carriers (TT, n=47). This is the first study to examine FTO-related brain differences in young children before obesity onset, suggesting the cerebellum may be a key structure in FTO-mediated obesity risk mechanisms.

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

This cross-sectional study of 792 Latin American subjects examined associations between FTO and IRX3 gene variants with obesity and metabolic disorders. While FTO and IRX3 SNPs were not in linkage disequilibrium, the TT genotype of rs9939609 (FTO) was associated with increased waist circumference (adj-p=0.01), and rs3751723 (IRX3) was associated with body weight excess (OR=1.06, adj-p=0.03). A FTO-IRX3 haplotype (G-A-A-T) was also associated with body weight excess (OR=0.67, p=0.04), suggesting gene-gene interaction effects independent of genetic ancestry.

Analysis of 27 FTO gene variants in 1,424 Hispanic Americans and 604 African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS) found multiple SNPs associated with BMI, waist circumference, and subcutaneous adipose tissue (p-values 0.001-0.05 in Hispanics), confirming FTO's role in overall fat mass rather than visceral fat distribution. Key variants rs9939609, rs8050136, rs1121980, rs1421085, rs17817449, and rs3751812 showed consistent associations with adiposity measures, with effect sizes of 0.3-2.4 kg/m² per allele for BMI in Hispanic Americans.

In 55 Europid participants, FTO mRNA expression in adipose tissue was 3-fold higher in subcutaneous versus visceral depots and showed significant negative correlations with BMI and body fat percentage. However, the obesity-associated SNP rs8050136 (in linkage disequilibrium with rs9939609) was not associated with FTO or RPGRIP1L mRNA expression levels in either adipose tissue depot.