The rs1801282;rs1805192" genes_norm="5468">Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPARG; NCBI dbSNP rs1801282) has been associated with preservation of cognitive function, decreased risk of diabetes, and increased risk of obesity.
Potential interactions between prenatal DHA and the peroxisome proliferator-activated receptor-γ (PPARγ) genotype as a measure of the genetic predisposition to obesity were investigated.
We examined 750 Danish men with juvenile-onset obesity (body mass index 33.3 +/- 2.4 kg/m(2)) and 706 control subjects (body mass index 21.4 +/- 2.1 kg/m(2)) for mutations in MC4R.
The coding region of the MC4R gene was sequenced in nonobese patients with binge-eating behavior diagnosed with bulimia nervosa or binge-eating disorder (n=77); individuals with severe early-onset obesity (n=170); and lean women with anorexia nervosa (n=20).
We also detected a novel mutation (L207V) in a severely obese 69-year-old female patient, although the mutation did not cosegregate with obesity in the corresponding pedigree and had no functional consequences on MC4R protein function.
Since haploinsufficiency has been proposed as a causal mechanism of obesity associated with these mutations, reduction in gene transcription caused by mutations in the transcriptionally essential regions of the MC4R promoter may also be a cause of severe obesity in humans.
In 1708 women of the EDEN mother-child cohort, the PPARγPro12Ala and C1431T polymorphisms were genotyped and analyzed in association with maternal prepregnancy body mass index, obesity before pregnancy, and gestational diabetes, separately and also combined in haplotypes.
In conclusion, the study demonstrates association of variants near MC4R with obesity and related traits in Indian children and adults, with higher impact during childhood.
These data provide support for two hypotheses: (i) that the majority of these rare, obesity-associated mutations are likely defective and causative of obesity and (ii) that β-arrestin recruitment is a valuable marker of normal MC4R function.
Here, we show that targeted PPARγ mutations resulting in constitutive deacetylation (K268R/K293R, 2KR) increased energy expenditure and protected from visceral adiposity and diet-induced obesity by augmenting brown remodeling of white adipose tissues.
Recently, the advent of genome-wide association studies led to the discovery of association of polymorphisms in the 3' region of the MC4R with obesity.
The relatively large effect of these common variants near melanocortin 4 receptor on general and visceral adiposity in childhood, especially in girls, could prove helpful in elucidating the molecular mechanisms underlying the development of obesity in early life.
We report here the first in-frame deletion mutation of the MC4R gene (delta88-92) in an obese female patient with onset of obesity at less than 5 yr of age.
Gender-specific effect of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma-2 gene on obesity risk and leptin levels in a Tunisian population.
Here, we investigated the expression of APM1 in adipose tissue and studied the relationship between variation in APM1 expression, the APM1 G276T polymorphism, the common PPARGPro12Ala polymorphism and clinical features of 36 morbidly obese (body mass index (BMI) 41.5 +/- 4.9 kg/m2) nondiabetic subjects.
This study aims to test whether 10 polymorphisms in obesity-related genes methionine sulfoxide reductase A (MSRA), transcription factor AP-2 beta (TFAP2B), melanocortin 4 receptor (MC4R), neurexin 3 (NRXN3), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A), transmembrane protein 18 (TMEM18), homolog of S. cerevisiae Sec16 (SEC16B), homeobox B5 (HOXB5) and olfactomedin 4 (OLFM4) are associated with the risk of obesity in Portuguese children.