Missense mutations and polymorphisms of the MC4R gene in Polish obese children and adolescents in relation to the relative body mass index

Nowacka‐Woszuk, Joanna; Cieślak, J.; Skowrońska, Bogda; Majewska, Katarzyna Anna; Stankiewicz, Witold; Fichna, Piotr; Świtoński, M.

doi:10.1007/s13353-011-0036-2

Cited by 14 publications

(8 citation statements)

References 14 publications

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“…Interestingly, Val103Ile has been considered an obesity-protective polymorphism and was observed in both groups, being the most frequent variant identified in our sample (2.9%). This observation is similar to previous studies in a Polish cohort and a sample of the South American population 17,31,32. Wang et al31 have performed a meta-analysis using six East Asian studies, where they found that the frequency of this variant was 2.9% (n=19,882) in subjects with obesity and 3.9% (n=35,373) in nonobese individuals.…”

Section: Discussionsupporting

confidence: 87%

Identification of the MC4R start lost mutation in a morbidly obese Brazilian patient

Fonseca¹,

Abreu²,

Zembrzuski³

et al. 2019

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Background Melanocortin 4 receptor gene ( MC4R ) is an important regulator of food intake, body weight, and blood pressure. Mutations in MC4R are associated with the most common form of nonsyndromic monogenic obesity. MC4R variations have an autosomal co-/dominant model of inheritance. MC4R screening could reveal individuals previously unrecognized with Mendelian form of obesity for further clinical management and genetic counseling. However, there are limited data regarding MC4R variants in patients with obesity from Brazil. The aim of this study was to screen the coding region of the MC4R gene in a Brazilian cohort of severely obese adults and to investigate the phenotype–genotype correlation within MC4R variant carriers. Methods This study comprised 157 adult participants, stratified according to the period of obesity onset. The first group included 97 patients with childhood-onset obesity (0–11 years) and the second group comprised 60 subjects with adolescence/youth-onset obesity (12–21 years). The entire coding region of MC4R gene was screened by Sanger sequencing. Results As a result, five previously described variants (Met1?, Ser36Thr, Val103Ile, Ile98=, and Phe202Leu) were identified. Met1? is a start lost codon variant, which affects the translation of MC4R . It was found in a female patient with childhood-onset obesity. We also compared the anthropometric and metabolic parameters between patients with MC4R missense variants (Ser36Thr, Val103Ile, and Phe202Leu) and noncarriers. Patients carrying MC4R variants had higher median of waist–hip ratio when compared to noncarriers ( P =0.048). These missense variants were also associated with hypertension ( P =0.014). Additionally, Val103Ile carriers had lower diastolic blood pressure and lower systolic blood pressure compared to noncarriers ( P =0.020 and P =0.065, respectively). Val103Ile was also associated with hypertension ( P =0.003). Conclusion This study showed the prevalence of MC4R variants in a cohort of Brazilian adults with severe obesity. We also identified significant phenotype differences between carriers and noncarriers of missense variants in our sample, suggesting an important role of MC4R on body fat distribution and blood pressure.

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Section: Discussionsupporting

confidence: 87%

Identification of the MC4R start lost mutation in a morbidly obese Brazilian patient

Fonseca¹,

Abreu²,

Zembrzuski³

et al. 2019

DMSO

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“…In other independent studies in Spanish children the frequencies of this polymorphism were lower than in other European countries [43,44,45]. The frequency of the Ile251Leu variation in our studied sample was 5.04% (6 children with abdominal obesity), which is higher than the observed values in other Spanish and Polish pediatric populations [28,43,44]. Heterozygous subjects for the Ile251Leu SNP showed higher levels of total cholesterol and LDL-cholesterol.…”

Section: Discussioncontrasting

confidence: 76%

Melanocortin-4 Receptor and Lipocalin 2 Gene Variants in Spanish Children with Abdominal Obesity: Effects on BMI-SDS after a Lifestyle Intervention

et al. 2019

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Mutations leading to a reduced function of the melanocortin-4 receptor (MC4R) exert a major gene effect on extreme obesity. Recently it was shown that the bone derived hormone lipocalin 2 (LCN2) binds to the MC4R and activates a MC4R dependent anorexigenic pathway. We identified mutations in both genes and screened the effects of MC4R and LCN2 mutations on eating behavior and weight change after a lifestyle intervention. One hundred and twelve children (11.24 ± 2.6 years, BMI-SDS 2.91 ± 1.07) with abdominal obesity participated in a lifestyle intervention. MC4R and LCN2 coding regions were screened by Sanger sequencing. Eating behavior was assessed at baseline with the Children Eating Behavior Questionnaire (CEBQ). We detected three previously described non-synonymous MC4R variants (Glu42Lys, Thr150Ile, and Arg305Gln) and one non-synonymous polymorphism (Ile251Leu). Regarding LCN2, one known non-synonymous variant (Thr124Met) was detected. Eating behavior was described in carriers of the MC4R and LCN2 mutation and in non-carriers. MC4R and LCN2 mutations were detected in 2.42% and 0.84%, respectively, of Spanish children with abdominal obesity. A number of subjects with functional mutation variants in MC4R and LCN2 were able to achieve a reduction in BMI-SDS after a lifestyle intervention.

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“…In some other studies, it was found that two MC4R variants are negatively correlated with the risk of obesity (27). These polymorphisms cause amino acid substitutions in codon 103 (V103I) and codon 251 (I251L) (27,28). Contrary to these findings, in our study V103I mutation was found equally in patients and controls and I251L mutation were not detected in both of the groups.…”

Section: Discussioncontrasting

confidence: 99%

Effects of MC4R, FTO, and NMB gene variants to obesity, physical activity, and eating behavior phenotypes

et al. 2016

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SummaryObesity is a major contributory factor of morbidity and mortality. It has been suggested that biological systems may be involved in the tendency to be and to remain physically inactive also behaviors such as food and beverage preferences and nutrient intake may at least partially genetically determined. Consequently, besides environment, genetic factors may also contribute to the level of physical activity and eating behaviors thus effect obesity. Therefore the aim of this study is to investigate the effect of various gene mutations on obesity, physical activity levels and eating behavior phenotypes. One hundred patients and 100 controls were enrolled to the study. Physical activity levels were measured with an actical acceloremeter device. Eating behaviors were evaluated using Three-Factor Eating questionnaire (TFEQ). Associations between eating behavior scores and physical characteristics were also evaluated. The information about other obesity risk factors were also collected. Mutations were investigated with PCR, direct sequencing and RealTime PCR. rs1051168, rs8050146 22778C > T mutations were found statistically significant in patients, rs1121980 was found statistically significant in controls. 21 mutations were found in MC4R and near MC4R of which 18 of them are novel and 8 of them cause amino acid change. In addition, it was found that, some obesity related factors and questions of TFEQ are associated with various investigated gene mutations. Any relation between gene mutations and physical activity levels were not detected. It is thought that, due to the genotype data and eating behaviors, it may be possible to recommend patients for proper eating patterns to prevent obesity. V C 2016 IUBMB Life, 68(10):806-816, 2016

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Missense mutations and polymorphisms of the MC4R gene in Polish obese children and adolescents in relation to the relative body mass index

Cited by 14 publications

References 14 publications

<p>Identification of the <em>MC4R</em> start lost mutation in a morbidly obese Brazilian patient</p>

<p>Identification of the <em>MC4R</em> start lost mutation in a morbidly obese Brazilian patient</p>

Melanocortin-4 Receptor and Lipocalin 2 Gene Variants in Spanish Children with Abdominal Obesity: Effects on BMI-SDS after a Lifestyle Intervention

Effects of MC4R, FTO, and NMB gene variants to obesity, physical activity, and eating behavior phenotypes

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