Prevalence of pathogenetic MC4R mutations in Italian children with early Onset obesity, tall stature and familial history of obesity

Santoro, Nicola; Cirillo, Grazia; Xiang, Zuoshuang; Tanas, Rita; Greggio, Nella Augusta; Morino, Giuseppe; Vottero, Alessandra; Salvatoni, Alessandro; Pietro, Mario Di; Balsamo, Antonio; Crinò, Antonino; Grandone, Anna; Haskell‐Luevano, Carrie; Perrone, Laura; Giudice, Emanuele Miraglia del

doi:10.1186/1471-2350-10-25

Cited by 24 publications

(18 citation statements)

References 32 publications

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“…However, the MC4R rs17782313 polymorphism did not reach the statistical significance as it had a lesser effect in this population and, even though a similar trend was observed. While several studies have reported statistically significant associations between the MC4R rs17782313 and BMI or obesity [2], [24], [25], [51], there are also studies that did not find a significant association [9], [52] or found stronger associations with weight than BMI [11] and even studies that have reported an association with higher height [9], [53], [54] and that this association may mask the effects on BMI despite being associated with higher weight. Our results are in agreement with this observation as we found statistically significant differences in weight and height (although very small in magnitude for height).In agreement with other studies [12], [13] we have also found additive effects of these polymorphisms in this population.…”

Section: Discussionmentioning

confidence: 99%

Statistical and Biological Gene-Lifestyle Interactions of MC4R and FTO with Diet and Physical Activity on Obesity: New Effects on Alcohol Consumption

et al. 2012

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BackgroundFat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood.ObjectiveTo investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake.MethodsAdherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed.ResultsFTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (P<0.05 for all). A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score) were significant and we observed a 7% per-allele increase of being obese (OR = 1.07; 95%CI 1.01–1.13). We found relevant statistical interactions (P<0.05) with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P = 0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P = 0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/−SE: −0.57+/−0.16 g/d per-score-allele; P = 0.001).ConclusionStatistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI.

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Section: Discussionmentioning

confidence: 99%

Statistical and Biological Gene-Lifestyle Interactions of MC4R and FTO with Diet and Physical Activity on Obesity: New Effects on Alcohol Consumption

et al. 2012

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“…The different criteria for obesity definition led to varied obese and nonobese groups, which were applied to estimate the OR without any correction. Different cutoff points (28,30,35,40 kg/m 2 , or 95th, 97th, 98th BMI percentile) were used for cases, whereas cutoff points (25, 22, or 30 kg/m 2 ) for controls varied as well. Besides, different sex ratios and age of individuals among studies might influence the effect magnitude of the V103I variant on obesity.…”

Section: Figurementioning

confidence: 99%

Association of the MC4R V103I Polymorphism With Obesity: A Chinese Case–control Study and Meta‐analysis in 55,195 Individuals

et al. 2010

Obesity

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Recently, large‐scaled studies suggested a negative association of the infrequent allele of the melanocortin‐4 receptor (MC4R) V103I polymorphism with obesity. We conducted a Chinese case–control study, meta‐analysis in East Asians and in all populations, in order to further assess the association between the V103I polymorphism and reduced body weight and to explore whether the association varies among different ethnic groups. We conducted a case–control study to analyze this polymorphism in 2,012 children of two independent study groups from Beijing, China, no association was found between the V103I polymorphism and obesity or obesity‐related phenotypes (P > 0.10). In the meta‐analysis of 3,526 individuals from six East Asian studies, I103 carriers had a 31% lower risk for obesity (odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50–0.94, P = 0.02). Subsequently, we performed a large meta‐analysis of the six East Asian studies and 31 studies of other ethnic groups, involving 55,195 individuals with 19,822 obese cases and 35,373 nonobese controls. In total, the individuals with I103 allele had a 21% lower risk for obesity (OR = 0.79, 95% CI: 0.71–0.88, P < 0.0001). In conclusion, this study confirmed and extended the previous findings, suggesting the MC4R V103I polymorphism is negatively associated with human obesity. It provides significant evidence for the association in East Asian populations. Further large‐scaled studies in East Asian populations are needed to validate the association.

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“…This mutation was found several times in both obese and lean populations (Lubrano-Berthelier et al 2003, Hainerova et al 2007, Nowacka-Woszuk et al 2011. This fact indicates that it may be one of the most prevalent MC4R mutations in Europe (Valli-Jaakola et al 2004, Hainerova et al 2007, Santoro et al 2009, Nowacka-Woszuk et al 2011.…”

Section: Mc4r Genotypesmentioning

confidence: 99%

Melanocortin-4 Receptor Gene Mutations in Obese Slovak Children

Staníková¹,

Sůrová²,

Tichá³

et al. 2015

Physiol Res

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The most common etiology of non-syndromic monogenic obesity are mutations in gene for the Melanocortin-4 receptor (MC485) with variable prevalence in different countries (1.2-6.3 % of obese children). The aim of our study was 1) to search for MC4R mutations in obese children in Slovakia and compare their prevalence with other European countries, and 2) to describe the phenotype of the mutation carriers. DNA analysis by direct Sanger sequencing of the coding exons and intron/exon boundaries of the MC4R gene was performed in 268 unrelated Slovak children and adolescents with body mass index above the 97th percentile for age and sex and obesity onset up to 11 years (mean 4.3±2.8 years). Two different previously described heterozygous loss of function MC4R variants (i.e. p.Ser19Alafs*34, p.Ser127Leu) were identified in two obese probands, and one obese (p.Ser19Alafs*34), and one lean (p.Ser127Leu) adult family relatives. No loss of function variants were found in lean controls. The prevalence of loss-of-function MC4R variants in obese Slovak children was 0.7 %, what is one of the lowest frequencies in Europe.

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Prevalence of pathogenetic MC4R mutations in Italian children with early Onset obesity, tall stature and familial history of obesity

Cited by 24 publications

References 32 publications

Statistical and Biological Gene-Lifestyle Interactions of MC4R and FTO with Diet and Physical Activity on Obesity: New Effects on Alcohol Consumption

Statistical and Biological Gene-Lifestyle Interactions of MC4R and FTO with Diet and Physical Activity on Obesity: New Effects on Alcohol Consumption

Association of the MC4R V103I Polymorphism With Obesity: A Chinese Case–control Study and Meta‐analysis in 55,195 Individuals

Melanocortin-4 Receptor Gene Mutations in Obese Slovak Children

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