The rs9939609 polymorphism of the fat mass and obesity-associated (FTO) gene has been widely associated with childhood obesity in several European cohorts.
This study investigated whether the combined effects of FTO and MC4R increase the risk of obesity in children and adolescents living in Northwest China.
In the association analysis between the FTO gene variant and risk of childhood obesity, compared with the rs1421085TT wide-type genotype, rs1421085 CC and CT/CC genotypes were associated with 59% and 71% increased risks of childhood obesity (adjusted OR = 1.59, 95%CI = 1.00-2.53 for CC; adjusted OR = 1.71, 95%CI = 1.10-2.65 for CT/CC), while the rs17817449 T > G variant was not associated with the significantly increased risk of childhood obesity.
Three known adult BMI-associated loci (FTO, MC4R and ADCY3) and one childhood obesity locus (OLFM4) reached genome-wide significance (PWald < 1.13 × 10(-8)) with BMI at 8 years and/or change over time.
The results indicated that variant in FTO gene was significantly associated with increased risk of overweight/obesity in children and adolescents (OR=1.35; 95%CI: 1.27-1.44; P<0.001).
The combined presence of three or more high-risk alleles of both the FTO and MC4R genes confers a 4-fold higher risk for obesity in children and adolescents of Greek origin, although these risk alleles have no impact on the metabolic alterations observed in these obese children and adolescents.
Children from The Western Australian Pregnancy Cohort (Raine; n=1,506) Study were genotyped at 17 genetic loci shown to be associated with childhood obesity (FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, SEC16B, LYPLAL1, TFAP2B, MTCH2, BCDIN3D, NRXN3, SH2B1, MRSA) and an obesity-risk-allele-score was calculated as the total number of 'risk alleles' possessed by each individual.
This meta-analysis shows that the FTOrs9939609 polymorphism in the gene is a risk factor for obesity in children and adolescents with the presence of the A allele, both homozygous genotype AA situation, as heterozygous AT.
These results suggest a gene-diet interaction between the MC3RC17A and G241A variants and a weight loss program for the ability to lose weight in childhood obesity.
In humans, Thr6Lys and Val81Ile variants of the melanocortin-3 receptor gene (MC3R) have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers.
MC3R and MC4R are involved in metabolic regulation and their gene variants are associated with severe pediatric obesity, whereas the function of MC5R remains to be fully elucidated.
ADIPOQ gene polymorphism rs1501299 interacts with fibre intake to affect adiponectin concentration in children: the GENe-Diet Attica Investigation on childhood obesity.
Common variants in the FTO locus, and near MC4R locus, have been shown to have a robust association with obesity in children and adults among various ethnic groups.
The prevalence of MC4R mutations was similar in patients developing obesity in childhood (2.83%; CI(95), 0.9-4.8) and in patients with a later onset of the disease (2.35%; CI(95), 0.9-3.8).
This result has implications for the potential pharmacologic rescue of childhood obesity-associated MC4R mutations and for the treatment of patients presenting with this condition.
In humans, the 6Lys-81Ile haplotype of melanocortin-3 receptor (MC3R) gene has been associated with childhood obesity, higher body fat percentage, and reduced fat oxidation compared to non-carriers.
Three known adult BMI-associated loci (FTO, MC4R and ADCY3) and one childhood obesity locus (OLFM4) reached genome-wide significance (PWald < 1.13 × 10(-8)) with BMI at 8 years and/or change over time.