The combined effect of MC4R and FTO risk alleles on childhood obesity in Greece

Lazopoulou, Natalia; Gkioka, Eleana; Ντάλλα, Ιωάννα; Pervanidou, Panagiota; Magiakou, Alexandra-Maria; Roma-Giannikou, Eleftheria; Chrousos, George P.; Papassotiriou, Ioannis; Dedoussis, George; Kanaka‐Gantenbein, Christina

doi:10.14310/horm.2002.1524

Cited by 18 publications

(24 citation statements)

References 41 publications

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“…The C/C genotype was significantly more frequent among individuals with higher BMI and WHtR values. This confirms the relationship between MC4R rs17782313 and obesity risk reviewed by Xi et al and evidenced by Lazopoulou in a European population of children . Despite the low MAF at PPARG rs1801282 and the previous contradictory results about its relationship with obesity , the PPARG G/G genotype resulted to be significantly associated with body overweight in our sample, confirming the results obtained in another young European population by Ochoa et al .…”

Section: Discussionsupporting

confidence: 92%

“…Even if a possible interaction among ACE , MC4R , FTO and PPARG genes can be inferred by GWASs, which supported their relation with obesity and overweight, previous investigations did not test the presence of synergistic effects using a targeted approach. However, it should be mentioned that several studies have been conducted on this topic; a longitudinal study from Bouwman et al reported that adult men carrying FTO rs9939609 T/T genotype + ACE rs4646994‐D allele were protected against weight gain over a 10‐year period; Lazopoulou et al showed a cumulative effect of the presence of FTO rs9939609‐A allele and MC4R rs17782313‐C allele on childhood obesity in a Greek population; Goni et al showed that carrying unfavorable genotypes at both FTO rs9939609 and MC4R rs17782313 loci can influence weight loss in response to a hypocaloric diet; Carlos et al failed to prove the interaction of FTO rs9939609 and PPARG rs1801282 with obesity in Portuguese women; Passaro et al demonstrated a gene–gene interaction between PPARG rs1801282 and ACE rs4646994 on BMI and fat mass.…”

Section: Discussionmentioning

confidence: 99%

“…Similar to FTO , MC4R regulates feeding control and energy balance . Rare MC4R loss‐of‐function mutations can cause monogenic forms of obesity , while the common variant rs17782313 has been consistently associated with obesity in European adults and children and, notably, it showed a synergistic effect with FTO on the obese phenotype . Another widely studied gene is the Peroxisome Proliferator‐Activated Receptor Gamma ( PPARG, OMIM*601487, on chr.…”

Section: Introductionmentioning

confidence: 99%

“…Here, we conducted a study on a population of 306 Italian children and adolescents, who regularly play sports, with the aim of replicating and extending previous findings on FTO rs9939609, MC4R rs17782313, PPARG rs1801282 and ACE rs4646994 polymorphisms. Considering previous evidence on the possible cumulative effect of some of the mentioned polymorphisms , we also tested the existence of epistatic phenomena and the cumulative risk conferred by the combinations of these polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

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Obesity‐related genetic polymorphisms and adiposity indices in a young Italian population

et al. 2017

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Pediatric obesity develops when a complex biological predisposition collides with an obesogenic environment. To further elucidate the role of genetics in obesity onset, we performed a candidate-gene association study in a young and sportive Italian population by testing the association of functional polymorphisms in ACE (rs4646994), FTO (rs9939609), MC4R (rs17782313) and PPARG (rs1801282) genes with body mass index (BMI) and waist-to-height ratio (WHtR). We also tested the combinations of identified risk genotypes and epistatic interactions among them to determine the existence of cumulative effects in predicting the predisposition to gain weight. Our results confirm a significant direct influence of MC4R rs17782313 and PPARG rs1801282 on body composition, that is, minor allele homozygotes showed significantly higher BMI (rs17782313, β = 1.258, P = 0.031; rs1801282, β = 6.689, P = 1.2 × 10 ) and WHtR (rs17782313, β = 0.021, P = 0.005; rs1801282, β = 0.069, P = 0.003) values. Moreover, by leveraging multifactor dimensionality reduction and general linear model (GLM) approaches we identified an epistatic interaction between ACE and MC4R, where heterozygosity at ACE rs4646994 seems to protect from the unfavorable predisposition to gain weight given by C/C genotype at MC4R rs17782313 (GLM, P = 0.004). In conclusion, to clarify the role of genetics in multifactorial diseases remains a difficult goal, even for the most investigated polymorphisms and in controlled populations. Further studies on epistasis and gene-gene interaction will help to elucidate this complex scenario. © 2017 IUBMB Life, 69(2):98-105, 2017.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Obesity‐related genetic polymorphisms and adiposity indices in a young Italian population

et al. 2017

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“…Many studies showed that the risk allele A of rs9939609 in FTO gene was associated with increase of the BMI and incidence of obesity (11)(12)(13) . The presence of both risk alleles A and C from rs9939609 in FTO gene and rs17782313 in MC4R gene respectively caused 4-fold increase of obesity risk in childhood and adolescents from Greece origin (14) . Luczyoski et al (15) showed that the main factors that caused an increase of BMI in children with Type 1 Diabetes, especially in female gender, are poor metabolic control and carrying the A allele of the rs9939609.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Single Nucleotide Polymorphism Rs9939609 in Fto Gene of Obese Males in Iraqi Population

2016

IJMS

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Background Obesity is a serious on public health. It contributes in many serious health conditions including high cholesterol, type 2 diabetes, osteoarthritis, high blood pressure, gallbladder disease, coronary heart disease, stroke, respiratory problems … etc. Polymorphism of TA (rs9939609) in fat mass and obesity associated (FTO) gene was found to be associated with obesity in children and adults according to many studies conducted on populations from Europe, America and Asia. Whether Single nucleotide polymorphism (SNP) rs9939609 is an associated with obesity in Iraqi population remains of concern. Objective To investigate the polymorphism of rs9939609 SNP in FTO gene and its relationship to the obese males in Iraqi population. Methods One hundred twenty of males were classified as obese based on body mass index (BMI) with mean age 20-50 year and fifty aged-matched healthy males as a control were included in this study. Lipid profile was estimated by using Spinreact-Сє, and an ELISA kit was used to assess the FTO level. Results The results showed that there are significant differences P ≤ 0.05 for AA genotype with all parameters whereas TA genotype showed significant differences with most of parameters in revers to TT genotype, which has showed no significant differences with most of parameters. The percentage of TT, TA, AA, alleles were 27.72%, 49.86%, 22.42% respectively, also an elevated of TT genotype frequency was observed in healthy compared to obese. On the other hand, the percentage of T and A allele frequency were 52.65% and 47.35% respectively. Also, an elevated in serum FTO enzyme level was observed in obese. Conclusion The presence of A risk allele in the Iraqi population is the cause in the incidence of obesity, which reflected its impact on the BMI and central obesity through the disturbances in lipid profile and FTO enzymes value.

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Association of the melanocortin 4 receptor gene rs17782313 polymorphism with rewarding value of food and eating behavior in Chilean children

et al. 2016

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Studies conducted in monozygotic and dizygotic twins have established a strong genetic component in eating behavior. Rare mutations and common variants of the melanocortin 4 receptor (MC4R) gene have been linked to obesity and eating behavior scores. However, few studies have assessed common variants in MC4R gene with the rewarding value of food in children. The objective of the study was to evaluate the association between the MC4R rs17782313 polymorphism with homeostatic and non-homeostatic eating behavior patterns in Chileans children. This is a cross-sectional study in 258 Chilean children (44 % female, 8-14 years old) showing a wide variation in BMI. Anthropometric measurements (weight, height, Z-score of BMI and waist circumference) were performed by standard procedures. Eating behavior was assessed using the Eating in Absence of Hunger Questionnaire (EAHQ), the Child Eating Behavior Questionnaire (CEBQ), the Three-Factor Eating Questionnaire (TFEQ), and the Food Reinforcement Value Questionnaire (FRVQ). Genotype of the rs17782313 nearby MC4R was determined by a Taqman assay. Association of the rs17782313 C allele with eating behavior was assessed using non-parametric tests. We found that children carrying the CC genotype have higher scores of food responsiveness (p value = 0.02). In obese girls, carriers of the C allele showed lower scores of satiety responsiveness (p value = 0.02) and higher scores of uncontrolled eating (p value = 0.01). Obese boys carrying the C allele showed lower rewarding value of food in relation to non-carriers. The rs17782313 C allele is associated with eating behavior traits that may predispose obese children to increased energy intake and obesity.

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The combined effect of MC4R and FTO risk alleles on childhood obesity in Greece

Cited by 18 publications

References 41 publications

Obesity‐related genetic polymorphisms and adiposity indices in a young Italian population

Obesity‐related genetic polymorphisms and adiposity indices in a young Italian population

Analysis of Single Nucleotide Polymorphism Rs9939609 in Fto Gene of Obese Males in Iraqi Population

Association of the melanocortin 4 receptor gene rs17782313 polymorphism with rewarding value of food and eating behavior in Chilean children

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