rs9930506

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 case-control study of 2,033 colorectal cancer cases and 9,640 controls investigated whether BMI and waist size susceptibility variants are associated with colorectal cancer risk. Two obesity SNPs showed significant associations: KCTD15 rs29941 (OR = 0.90, p = 0.01) was protective, while MC4R rs17782313 (OR = 1.12, p = 0.02) increased risk. However, neither association remained significant after multiple comparisons correction, and overall obesity variants showed minimal effects on colorectal cancer.

This longitudinal study examined FTO gene SNPs in 658 white subjects from childhood to adulthood. While FTO SNPs showed no significant association with birth weight or longitudinal BMI during childhood, three SNPs (rs9939609, rs17820875, and rs860713) were significantly associated with longitudinal BMI in adulthood (P = 5.3×10⁻⁵, 2.0×10⁻⁴, and 0.001, respectively). The study also identified interactions between birth weight and FTO variants, showing that lower birth weight predisposes to higher adult BMI depending on FTO risk genotypes.

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.

This study examined 704 Old Order Amish individuals and identified 26 FTO gene variants associated with BMI (P=.04 to <.001), with rs1861868 (0.75 BMI increase per A allele, P<.001) and rs1477196 (0.84 BMI increase per C allele, P<.001) showing the strongest associations. Notably, the study found a significant gene-by-environment interaction where increased physical activity substantially blunted the effects of FTO variants on body weight, suggesting that genetic predisposition to obesity can be mitigated through adequate physical activity.

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.