rs17782313

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 doctoral thesis examines the role of physical activity, physical fitness, and exercise on immunometabolism during pregnancy across six studies in overweight/obese pregnant women. In the genetic analysis (n=81), neonatal birth weight was significantly greater in mothers carrying the CC genotype at rs6567160 and rs17782313 in the MC4R gene, though gestational weight gain was not influenced by maternal FTO or MC4R genotypes.

Association study of 35 GWAS-identified body mass SNPs in 949 elderly Swedish participants (mean age 70-75 years). Significant association found between rs10968576 (LINGO2, intron 4) and BMI with a larger effect size (β = 0.69 kg/m²) than reported in younger populations, suggesting age-specific genetic effects on body mass in the elderly.

This study investigated common genetic variation in the MC4R gene region in American Indians (n=7,081) and found that rs74861148 and rs483145 were independently associated with increased BMI in adults (β=0.68 kg/m² and β=0.58 kg/m², respectively), with a combined G-A haplotype showing the strongest association (β=0.89 kg/m², p=5.5×10⁻⁷). Additionally, the promoter SNP rs11872992 was nominally associated with BMI and showed a 12% reduction in MC4R promoter activity in vitro, and was associated with increased food intake (β=676 kcal/day, p=0.007) and decreased energy expenditure (β=-53.4 kcal/day, p=0.054).

This literature review examines the influence of genetic polymorphisms on obesity development and adaptive responses to physical activity, focusing on five candidate genes: COMT (rs4680, Val158Met), DRD2 (rs1800497 Taq1A and rs1799732), FABP2 (rs1799883, Ala54Thr), FTO (rs9939609, A/T), and UCP1 (rs1800592, A-3826G). The review synthesizes molecular mechanisms, phenotypic associations, and implications for human health and training adaptations, noting that physical activity reduces the FTO genetic effect on obesity risk by 30-80% and that various polymorphisms show differential impacts on body composition and metabolic responses to exercise.

This mechanistic study investigated whether aging impairs cerebral insulin resistance through defects in blood-brain barrier transport or neural signaling. In 160 human subjects, CSF/serum insulin ratios were reduced with age. Mouse experiments showed that aged mice had impaired brain AKT phosphorylation and cortical activity after peripheral insulin injection, but responses were intact after direct intracerebroventricular insulin injection, suggesting age-related impairment of insulin transport across the blood-brain barrier contributes to cognitive decline.

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.

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).

Genome-wide association study examining common variants near BDNF (rs6265, rs925946) and SH2B1 (rs7498665) in relation to snacking behavior across three European cohorts (French obese children, Swiss obese, D.E.S.I.R.). The study reports nominal evidence of association, with rs925946 in BDNF showing OR=1.21 (p=5.03×10⁻³) in the D.E.S.I.R. cohort and rs7498665 in SH2B1 showing OR=1.17 (p=9.57×10⁻³) in the Swiss cohort.

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.

Genome-wide association study of 139 antipsychotic-naïve pediatric patients identified common variants near the MC4R gene (melanocortin 4 receptor) on chromosome 18 associated with severe antipsychotic drug-induced weight gain. The most significant SNPs (rs489693, rs646749, rs12970134) showed p-values ranging from 2.80E-07 to 3.26E-06 in the discovery cohort and replicated in three additional cohorts (n=73, 40, 92). Minor allele homozygotes of rs489693 exhibited significantly greater increases in body fat mass, triglycerides, leptin, insulin, and HOMA-IR.

Meta-analysis of 19 studies (34,195 cases, 89,178 controls) confirmed that the rs17782313 polymorphism near the MC4R gene is associated with type 2 diabetes risk in Europeans and Asians (OR 1.10, 95% CI 1.07-1.13, p=2.83×10⁻¹²). The association remained significant after BMI adjustment (OR 1.06, 95% CI 1.03-1.09, p=2.14×10⁻⁵), suggesting an effect independent of obesity.

This case-control study of 1,146 Vietnamese preschool children (360 obese, 786 controls) examined LEP and LEPR gene variants in childhood obesity risk. SNP rs7799039 (LEP) showed significant association with obesity protection: the dominant model (AG+GG vs AA) had OR=0.713 (95% CI: 0.549-0.926, p=0.011), and the additive model showed 24.6% risk reduction per G allele (p=0.017). SNP rs1137101 (LEPR) showed no significant association. Gene-gene interaction analysis found the LEP_LEPR haplotype AG_GG reduced obesity risk by OR=0.687 (95% CI: 0.497-0.951, p=0.024) compared to AA_GG.

A comprehensive review of nutrigenetics and nutrigenomics examining how genetic variants influence individual responses to nutrients and dietary interventions. The paper discusses associations between numerous SNPs (rs9939609 in FTO, rs2287019 in GIPR, rs7903146 in TCF7L2, rs5219 in KCNJ11, and many others) and metabolic traits including obesity, type 2 diabetes, and other chronic diseases, along with epigenetic mechanisms by which phytochemicals (curcumin, resveratrol, lycopene) modulate gene expression. The review synthesizes current evidence for precision nutrition approaches tailored to individual genetic profiles.

This study tests the thrifty genotype hypothesis by examining 17 confirmed type 2 diabetes susceptibility loci and 13 obesity-susceptibility loci for signatures of positive selection. Using ancestral/derived allele analysis, integrated haplotype scores (iHS), and population differentiation (FST), the authors found limited evidence supporting the thrifty genotype hypothesis. Only rs7901695 at TCF7L2 showed notably elevated FST values (0.579 between JPT+CHB and YRI populations), and FTO showed the strongest selection signal among obesity loci (iHS=1.991).

This prospective study examined the combined effects of FTO rs1421085 and MC4R rs17782313 obesity risk alleles in two large European cohorts (4,762 Finnish adolescents and 3,167 French adults). Subjects carrying 3-4 risk alleles had a 3-fold increased obesity susceptibility in childhood and 1.8-fold increased risk in adults (OR=1.21, p=0.02), with each additional risk allele increasing fat mass by 0.48% (p=0.001). The effects on type 2 diabetes were mediated through BMI. MC4R showed stronger male-specific effects and FTO effects were accentuated by low physical activity.