Dataset Information

Association of the melanocortin-4 receptor V103I polymorphism with dietary intake in severely obese persons.

ABSTRACT: Several studies have reported that carriers of the 103I allele of the melanocortin-4 receptor (MC4R) gene had lower body weight than did persons with the wild-type genotype. A recent study found an association of the MC4R 103I variant with carbohydrate intake, which may mediate some of the association of this variant with leanness.The purpose of the study was to investigate the association between the MC4R V103I polymorphism and the dietary intake of persons with severe obesity, which was derived by using the Willett food-frequency questionnaire.The MC4R V103I polymorphism was genotyped in a group of 1029 severely obese white subjects with an average body mass index (BMI; in kg/m(2)) of 46.0 (range: 33-92).Carriers of the 103I allele had significantly higher daily energy (364 kcal/d or 19%; P = 0.03) and carbohydrate (57 g/d or 27%; P = 0.01) intakes than did noncarriers, but there was no relation with BMI. No notable association of this polymorphism with lipid and glucose variables of the metabolic syndrome was observed.The higher dietary intake of carbohydrates in severely obese persons with the MC4R 103I variant is in line with previous findings. It may indicate a differential effect on body size measures in extremely obese subjects as compared with the general population.

SUBMITTER: Pichler M

PROVIDER: S-EPMC3246117 | biostudies-other | 2008 Sep

REPOSITORIES: biostudies-other

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Association of the melanocortin-4 receptor V103I polymorphism with dietary intake in severely obese persons.

Pichler Michaela M Kollerits Barbara B Heid Iris M IM Hunt Steven C SC Adams Ted D TD Hopkins Paul N PN Kronenberg Florian F

The American journal of clinical nutrition 20080901 3

<h4>Background</h4>Several studies have reported that carriers of the 103I allele of the melanocortin-4 receptor (MC4R) gene had lower body weight than did persons with the wild-type genotype. A recent study found an association of the MC4R 103I variant with carbohydrate intake, which may mediate some of the association of this variant with leanness.<h4>Objective</h4>The purpose of the study was to investigate the association between the MC4R V103I polymorphism and the dietary intake of persons ...[more]

PMID: 18779298

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Project description:Background and aimThe association with obesity of a common variant near the melanocortin-4 receptor (MC4R) gene (rs17782313) has been indicated in various studies. Adherence to dietary quality indices also have shown to have potential favorable effects on obesity-related health outcomes. However, no study has examined the interaction between rs17782313 and the Dietary Approach to Stop Hypertension (DASH) score and the Mediterranean Dietary Score (MDS) on cardio-metabolic risk factors and hypothalamic hormones. Therefore, the purpose of the current study was to examine whether adherence to these dietary quality indices modifies the association of the MC4R rs17782313 polymorphism with cardio-metabolic risk factors and hypothalamic hormones among obese adults.MethodTwo hundred eighty-eight healthy obese adults were recruited in this cross-sectional study. Diet quality indices, including DASH score and MDS, were calculated from a validated 147-item food frequency questionnaire (FFQ). MC4R s17782313 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An ANCOVA multivariate interaction model was used to assess the gene-diet interaction.ResultsSignificant interactions were detected between DASH score and MC4R rs17782313 genotypes on systolic blood pressure (SBP), atherogenic index of plasma (AIP), and serum glucose and triglyceride (TG) among the female group (pInteraction < 0.05). In the male group, there were gene-DASH and gene-MDS interactions in relation to serum glucose concentration and plasma α-melanocyte stimulating hormone (MSH) levels, but these were found only in multi-adjusted interaction models (pInteraction < 0.05). In addition, there was a significant interaction between MC4R rs17782313 polymorphism and DASH score on plasma agouti-related peptide (AgRP) concentrations in the female group in a multivariate interaction model (pInteraction < 0.05). An inverse association between DASH score and chance of having the CC genotype in a multivariate-adjusted model among women was also revealed.ConclusionMC4R rs17782313 interacts with healthy dietary pattern (DASH score and MDS) to influence cardio-metabolic risk factors and hypothalamic hormones in obese individuals. Prospective cohort studies are needed to further assess these findings.

Project description:BACKGROUND:Controversial data is available on the effect of the Melanocortin-4 receptor (MC4R) gene variation on metabolic syndrome (MetS) and ineffectiveness of diet in managing MetS. Effects of the interaction between MC4R polymorphism and dietary factors on MetS were investigated in this study. METHODS:Subjects of this nested case-control study were selected from among participants of Tehran Lipid and Glucose Study. Each case (n?=?815) was pair matched randomly with a control by age (±5 years) and sex from among those who had not developed ?1 MetS components at the time that the corresponding case developed MetS. Dietary patterns were determined using factor analysis on 25 foods groups using a valid and reliable, 168-item semi-quantitative food frequency questionnaire (FFQ). MC4R rs12970134 were genotyped by Tetra-Primer ARMS-polymerase chain reaction analysis. Adjusted conditional logistic regression was used to estimate the interactions of SNP with quartiles of dietary factors in relation to MetS. MetS was defined by the modified National Cholesterol Education Program/Adult Treatment panel III. RESULTS:Two dietary patterns were extracted. The healthy dietary pattern was loaded heavily on vegetables, legumes, low fat dairy, whole grains, liquid oils and fruits; the western dietary pattern consisted of a high intake of soft drinks, fast foods, sweets, solid oils, red meats, salty snacks, refined grains, high fat dairy, tea and coffee, eggs and poultry. Among A allele carriers, being in the highest quartiles of western dietary pattern score and saturated fatty acid intake had an increased risk of MetS, compared to those in the lowest quartile (P trend?=?0.007). Saturated fatty acid intake could modulate the association of A allele carriers of MC4R with MetS (P interaction?=?0.03). A significant interaction was observed between rs12970134 with total fat and iron intake on the risk of abdominal obesity (P interaction?<?0.05). CONCLUSION:Our findings suggest an interaction between rs12970134 and western dietary pattern, fat and vegetable intakes on the risk of MetS or its components.

Project description:BACKGROUND: At present pathogenic mechanisms of cancer cachexia are poorly understood. Previous evidence in animal models implicates the melanocortin-4 receptor gene (MC4R) in the development of cancer cachexia. In humans, MC4R mutations that lead to an impaired receptor function are associated with obesity; in contrast, the most frequent polymorphism (Val103Ile, rs2229616; heterozygote frequency approximately 2%) was shown to be negatively associated with obesity. We tested if cancer patients that are homo-/heterozygous for the Val103Ile polymorphism are more likely to develop cachexia and/or a loss of appetite than non-carriers of the 103Ile-allele. METHODS: BMI (body mass index in kg/m2) of 509 patients (295 males) with malignant neoplasms was determined; additionally patients were asked about premorbid/pretherapeutical changes of appetite and weight loss. Cachexia was defined as a weight loss of at least 5% prior to initiation of therapy; to fulfil this criterion this weight loss had to occur independently of other plausible reasons; in single cases weight loss was the initial reason for seeing a physician. The average age in years (+/- SD) was 59.0 +/- 14.5 (males: 58.8 +/- 14.0, females 59.2 +/- 14.0). Blood samples were taken for genotyping of the Val103Ile by PCR- RFLP. RESULTS: Most of the patients suffered from lymphoma, leukaemia and gastrointestinal tumours. 107 of the patients (21%) fulfilled our criteria for cancer cachexia. We did not detect association between the Val103Ile polymorphism and cancer cachexia. However, if we exploratively excluded the patients with early leucaemic stages, we detected a trend towards the opposite effect (p < 0.05); heterozygotes for the 103Ile-allele developed cancer cachexia less frequently in comparison to the rest of the study group. Changes of appetite were not associated with the 103Ile-allele carrier status (p > 0.39). CONCLUSION: Heterozygotes for the 103Ile-allele are not more prone to develop cancer cachexia than patients without this allele; possibly, Ile103 carriers might be more resistant to cancer cachexia in patients with solid tumors. Further studies of the melanocortinergic system in cachexia of patients with solid tumors are warranted.

Dataset Information

Association of the melanocortin-4 receptor V103I polymorphism with dietary intake in severely obese persons.

Publications

Association of the melanocortin-4 receptor V103I polymorphism with dietary intake in severely obese persons.

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