rs3751812

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.

In a population-based cohort of 3,179 children, the study tested two weighted genetic risk scores based on 15 childhood and 97 adult BMI-associated SNPs, plus ten individual appetite/satiety SNPs, for association with eating behavior measures. The 97 SNP adult BMI risk score was nominally associated with lower satiety responsiveness (β: -0.007 SD, 95% CI -0.013, 0.000), while individual SNPs rs11030104 (BDNF) and rs10733682 (LMX1B) showed nominal associations with reduced satiety responsiveness (β: -0.057 to -0.087 SD). Overall, findings do not strongly support that BMI-associated SNPs influence eating behavior at this young age.

This scoping review examined 18 observational studies (n=26,684) from low- and middle-income countries investigating gene-environment interactions affecting obesity risk. The review found statistically significant associations for 12 individual SNPs including FTO rs1421085, rs9939609, rs10163409, rs3751812, MC4R rs17782313, rs12970134, TMEM18 rs7561317, NEGR1 rs2815752, CARTPT rs2239670, UCP2 rs659366, CLOCK rs1801260, and FLJ33544 rs140133294, though most associations were not replicated across different populations and environmental exposures.

This study examined 8 adult obesity-susceptibility loci in 7,225 children aged 2-18 years using quantile regression to assess whether genetic effects on BMI are uniform across the BMI distribution. The authors found that obesity risk alleles (FTO rs3751812, MC4R rs12970134, TMEM18 rs2867125, BDNF rs6265, SEC16B rs10913469, GNPDA2 rs13130484, NRXN3 rs10146997, and TNNI3K rs1514175) were more strongly associated with BMI increases at the upper tail of the distribution (85th-95th percentiles, β=0.06-0.11, p<10^-6) compared to the lower tail, suggesting that standard linear regression approaches may underestimate genetic effects on childhood obesity.

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

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.

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.