MC4R Rs17782313 Research Articles

The role of MC4R rs17782313 gene polymorphism, anthropometric and bioimpedance parameters in the etiology of pregnant woman's obesity

The role of MC4R rs17782313 gene polymorphism, anthropometric and bioimpedance parameters in the etiology of pregnant woman's obesity

Fat Mass and Obesity-Related Gene Variants rs9939609 and rs7185735 are Associated with Second-Generation Antipsychotic-Induced Weight Gain

Weight gain is a limiting and frequent adverse effect of second-generation antipsychotic therapy. Identifying genetic risk factors would significantly improve pharmacotherapy. We focused on rs7185735 and rs9939609, 2 common single nucleotide polymorphisms of the fat mass and obesity-associated (FTO) gene reported to be associated with obesity. Three-hundred fifty Caucasian inpatients were included in a naturalistic study. After 4 weeks of treatment, we did not observe any significant association of polymorphisms with weight change in the whole study population (p>0.05). In a subpopulation without additional weight-inducing comedication (n=178), G-allele carriers of rs7185735 gained 3.4 times more weight (1.69 kg±3.1 kg, p=0.019) than AA genotypes (0.49 kg±3.1 kg). A-allele carriers of rs9939609 gained 3.1 times more weight (1.65 kg±3.1 kg, p=0.029) than TT genotypes (0.54 kg±3.2 kg). Our findings confirm the role of the FTO gene as a high-potential risk factor for obesity and indicate a value for predicting a weight gain induced by second-generation antipsychotics. Further, we detected an additive effect of FTO rs7185735 and MC4R rs17782313.

Nutrigenetic variants and cardio-metabolic risk in women with or without gestational diabetes

AimGestational diabetes mellitus (GDM) is the most frequent metabolic disorder in pregnancy and it can be considered a silent risk associated to T2DM and CVD later in life. The aim of this study was to investigate the association of clinical parameters with nine single nucleotide polymorphisms (SNPs) involved with nutrients and metabolism in women with or without GDM in order to identify potential routine clinical markers for early prevention. MethodsNine gene variants associated with nutrients and metabolism, namely PPARG2 rs1801282 (C > G); PPARGC1A rs8192678 (C > T); TCF7L2 rs7903146 (C > T); LDLR rs2228671 (C > T); MTHFR rs1801133 (C > T); APOA5 rs662799 (T > C); GCKR rs1260326 (C > T); FTO rs9939609 (T > A); MC4R rs17782313 (T > C) were genotyped in 104 GDM cases and 124 controls using High Resolution Melting (HRM) analysis. ResultsThe genetic variant rs7903146 (C > T) in TCF7L2 gene showed a strong association with GDM risk (OR: 2.56; 95% CI: [1.24–5.29]). Moreover, a significant correlation was observed between lipid parameters and polymorphisms in other genes, namely PPARG2 [p = 0,03], APOA5 [p = 0,02], MC4R [p = 0,03], LDLR [p = 0,04] and FTO [p = 0,03]. In addition, rs17782313 variant, mapped close to MC4R gene, was associated to BMI in pre-pregnancy [p = 0,02] and at the end of pregnancy [p = 0,03] in GDM group. ConclusionIn our study, we found significant associations between routine clinical parameters and some gene variants connected with nutrients and metabolism in women with GDM. These results can provide useful information to develop effective tools and possible personalized intervention strategies in a timely manner.

Searching for Factors Raising the Incidence of Metabolic Syndrome Among 45-60-Year-Old Women.

Metabolic syndrome is an increasing health problem, whose pathogenesis may be associated with genetic factors. The main purpose of our study was to assess relationships between MetS and the presence of the FTO rs9939609, the MC4R rs17782313, and the PPAR-γ rs1801282 polymorphisms in 45-60-year-old women. The study included patients from the general population of the Westpomeranian Province (Poland). The mean age was 54.3 ± 4.2 years. The research procedure involved taking structured history, physical examination, anthropometric measurements, and collecting blood for biochemical and genetic analysis. The patients who met the diagnostic criteria for MetS constituted 38.35% of all participants (sample size: 425 patients). The comparison of blood biochemical parameters revealed numerous differences between the women with MetS and those from the control group. Genetic analysis demonstrated that the T allele of the FTO gene was a factor substantially decreasing the incidence of MetS in the study sample (ORT vs. A = 0.734; 95% CI: 0.555 - 0.970; p < 0.05). Other polymorphisms were not directly related to MetS incidence. Conclusions: 1. MetS-related abnormalities are widespread in the population of 45-60-year-old Polish women. Those most common are the elevated serum total cholesterol and LDL levels, increased insulin resistance and BMI scores, as well as visceral obesity. 2. No direct relationships were demonstrated between MetS and the gene polymorphisms analyzed in our study except for the FTO rs9939609, whose A allele and A/A genotype seemed to predispose to metabolic disorders.

Polymorphisms in Genes Involved in the Leptin-Melanocortin Pathway are Associated with Obesity-Related Cardiometabolic Alterations in a Southern Chilean Population.

Polymorphisms in genes encoding proteins of the leptin-melanocortin pathway have been associated with obesity. The involvement of these polymorphisms with changes in body mass index (BMI) and anthropometric measures could also imply a contribution to the risk of metabolic syndrome (MetS) and metabolic alterations. We evaluated the relationship of leptin-melanocortin system polymorphisms with obesity, MetS, and other metabolic alterations in Southern Chilean individuals. Two-hundred individuals were grouped as normoweight (BMI 18.0-24.9kg/m2), overweight (BMI 25.0-29.9kg/m2), and obese (BMI≥30kg/m2) or according to MetS status. Anthropometric measures (BMI, abdominal circumference, waist-to-hip ratio [WHR]) and biochemical parameters (glycemia and lipid profile) were evaluated. Polymorphisms LEP rs7799039, LEPR rs1137101, MC3R rs3746619 and rs3827103, and MC4R rs17782313 were evaluated by real-time PCR using allelic discrimination assays. LEPR rs1137101 GG genotype was related to reduced risk of obesity (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.08-0.79; p=0.018) and MetS (OR 0.36, 95% CI 0.15-0.88; p=0.024), but it was not significant after Bonferroni correction for multiple tests as compared to the AA genotype (p>0.01). Moreover, LEPR rs1137101 allele G (AG+GG) was related to lower BMI and WHR (p<0.01). Further multiple linear regression analysis demonstrated that this genotype was also responsible for reduced BMI in 2.44kg/m2 and WHR in 0.033 units. MC4R rs17782313 allele C (TC+CC) was slightly associated with diminished risk of MetS (OR 0.48, 95% CI 0.23-0.98; p=0.040) and reduced BMI values in 1.95kg/m2 (p<0.05). Regarding lipid profile, LEPR rs1137101 allele G carriers had lower triglycerides and very-low-density lipoprotein (VLDL) cholesterol, whereas individuals carrying the MC4R rs17782313 allele C had higher high-density lipoprotein (HDL) cholesterol (p<0.01). LEP rs7799039 allele A (GA+AA) was slightly associated with reduced total and low-density lipoprotein (LDL) cholesterol (p<0.05). These results suggest that polymorphisms at LEP, LEPR, and MC4R may be useful biomarkers of obesity-related cardiometabolic alterations in our population.

Metabolic biomarkers and gallstone disease – a population-based study

Objectives: The objectives for this study were to examine the associations between metabolic biomarkers of obesity including insulin resistance, vascular dysfunction, systemic inflammation, genetic susceptibility and ultrasound proven gallstone disease or cholecystectomy in a population-based cross-sectional study.Material and methods: A total of 2650 participants were included, of whom 422 had gallstone disease. Associations between selected metabolic biomarkers and gallstone disease were estimated by multivariable logistic regression models and expressed as odds ratio (OR) and 95% confidence interval (CI).Results: Gallstone disease was associated with fasting glucose (OR 1.14, 95% CI [1.05;1.24]), fasting insulin (OR 1.03, 95% CI [1.01;1.05]), homeostasis model assessment insulin resistance (OR 1.18, 95% CI [1.02;1.36]), the metabolic syndrome (OR 1.51, 95% CI [1.16;1.96]), white blood cell count (OR 1.07, 95% CI [1.00;1.15]) and C-reactive protein (OR 1.03, 95% CI [1.01;1.05]). A tendency towards an association for soluble urokinase plasminogen activator receptor was also found (OR 1.08, 95% CI [0.99;1.18]). The MC4R(rs17782313) (OR 1.27, 95% CI [1.02;1.58]), MAP2K5(rs2241423) (OR 1.80, 95% CI [1.04;3.41]), NRXN3(rs10146997) (OR 1.26, 95% CI [1.01;1.57]), HHEX(rs1111875) (OR 1.29, 95% CI [1.03;1.62]), FAIM2(rs7138803) (OR 0.66, 95% CI [0.48;0.91]), and apolipoprotein E4 allele (OR 0.76, 95% CI [0.59;0.98]) were associated with gallstone disease. Urinary albumin was not associated with gallstone disease. The association between BMI and gallstone disease was explained by insulin resistance.Conclusions: Biomarkers of insulin resistance, systemic inflammation and genetic obesity or type 2 diabetes risk alleles seem to be associated with gallstone disease. Future studies should explore temporal associations and genetic associations in other populations in order to clarify targets for prevention or intervention.

Gene-gene interaction on central obesity in school-aged children in China

Objective: To investigate possible effect of 6 obesity-associated SNPs in contribution to central obesity and examine whether there is an interaction in the 6 SNPs in the cause of central obesity in school-aged children in China. Methods: A total of 3 502 school-aged children who were included in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study were selected, and based on the age and sex specific waist circumference (WC) standards in the BCAMS study, 1 196 central obese cases and 2 306 controls were identified. Genomic DNA was extracted from peripheral blood white cells using the salt fractionation method. A total of 6 single nucleotide polymorphisms (FTO rs9939609, MC4R rs17782313, BDNF rs6265, PCSK1 rs6235, SH2B1 rs4788102, and CSK rs1378942) were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster City, CA, USA). Logistic regression model was used to investigate the association between 6 SNPs and central obesity. Gene-gene interactions among 6 polymorphic loci were analyzed by using the Generalized Multifactor Dimensionality Reduction (GMDR) method, and then logistic regression model was constructed to confirm the best combination of loci identified in the GMDR. Results: After adjusting gender, age, Tanner stage, physical activity and family history of obesity, the FTO rs9939609-A, MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity under additive genetic model (OR=1.24, 95%CI: 1.06-1.45, P=0.008; OR=1.26, 95%CI: 1.11-1.43, P=2.98×10(-4); OR=1.18, 95% CI: 1.06-1.32, P=0.003). GMDR analysis showed a significant gene-gene interaction between MC4R rs17782313 and BDNF rs6265 (P=0.001). The best two-locus combination showed the cross-validation consistency of 10/10 and testing accuracy of 0.539. This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated. Moreover, the combination of MC4R rs17782313-C and BDNF rs6265-G was associated with an increased risk of central obesity after adjustment for gender, age, Tanner stage, physical activity and family history of obesity. Conclusions: Our study showed that FTO rs9939609-A, MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity, and statistical interaction between MC4R rs17782313-C and BDNF rs6265-G increased risk of central obesity in school-aged children in China.

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

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 × 10-4 ) 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.

Relationships between FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men - a preliminary study.

PurposeMetabolic disorders, including MetS, obesity, and lipid disorders, may be related to genetic factors. Metabolic disorders are associated with decreased TS levels in aging men. The aim of this study was to evaluate the relationship between FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms and the presence of MetS and its components, the concurrent lipid disorders, as well as sex hormone concentrations.Subjects and methodsThis study involved 272 men of Caucasian descent aged 50–75 years. Lipid profile, including TCh, LDL, HDL, and TG, was evaluated by spectrophotometric method. Anthropometric measurements concerned WC and blood pressure. MetS was diagnosed according to the criteria of the IDF. Sex hormone profile, including TST, FTS, E2, DHEAS, and SHBG, was examined using enzyme-linked immunosorbent assay. Polymorphisms within FTO, MC4R, and PPARγ genes were identified using polymerase chain reaction-restriction fragments length polymorphism.ResultsThis study did not show links between the analyzed genetic polymorphisms and the presence of MetS, T2DM, HT, and obesity. However, higher concentrations of TCh and LDL were found in men with the FTO rs9939609 polymorphism in the recessive mode of inheritance (P=0.03 and P=0.05, respectively). Lower WC was found to be associated with MC4R rs17782313 gene inherited in the same model (P=0.005).ConclusionFTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms seem to have little effect on the incidence of metabolic malfunctions and no effect on androgen-related disorders in the examined middle-aged and elderly men.

LBPS 01-07 STUDY OF 6 BMI-ASSOCIATED LOCI IDENTIFIED IN GWAS FOR INTERACTIVE ASSOCIATIONS WITH CENTRAL OBESITY IN THE CHINESE CHILDREN

Objective: Recent genome-wide association studies have identified many single nucleotide polymorphisms (SNPs) associated with body mass index (BMI)/generalized obesity. In this study, we aimed to evaluate the interactive associations of identified SNPs with risk of central obesity in a child population from China. Design and Method: We genotyped 6 SNPs (FTO rs9939609, MC4R rs17782313, BDNF rs6265, PCSK1 rs6235, SH2B1 rs4788102, CSK rs1378942) in the Chinese children (N = 3502, age range 6–18 years) from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS). Based on the age- and sex- specific waist circumference (WC) standards generated in the BCAMS study, 1196 central obese cases and 2306 controls were identified. We analyzed gene-gene interactions among 6 polymorphic loci using the Generalized Multifactor Dimensionality Reduction (GMDR) method, and then used logistic regression models to confirm the best combination of loci identified in the GMDR. Results: GMDR analysis showed a significant gene-gene interaction between the rs17782313 polymorphism in the MC4R gene and the rs6265 polymorphism in the gene BDNF. The best two-locus combination scored 10 for cross-validation consistency and 10 for sign test (P = 0.0010). This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated. Moreover, the combination of the MC4R rs17782313 and the BDNF rs6265 was associated with a significantly increased risk of central obesity (OR = 1.48, 95% CI:1.25–1.74; P = 3.70 × 10–6) after adjustment for sex, age, pubertal stage, physical activity and family history of obesity. Conclusions: Our study showed the statistically interactive association between the MC4R rs17782313 and the BDNF rs6265 with risk of central obesity in the Chinese children, revealing that these genes affect obesity more likely through a complex interaction pattern than single gene effect.

High body mass index and risk of exacerbations and pneumonias in individuals with chronic obstructive pulmonary disease: observational and genetic risk estimates from the Copenhagen General Population Study.

In the clinic, the combination of obesity and chronic obstructive pulmonary disease (COPD) has been increasing. However, whether high body mass index (BMI) affects the risk of exacerbations and pneumonias in individuals with COPD is presently unknown. Genetics can be used to assess the causal role of high BMI in exacerbations and pneumonias in individuals with COPD. We tested the hypothesis that high BMI is associated with an increased risk of exacerbations and pneumonias in individuals with COPD, both observationally and genetically. We genotyped 93 894 individuals of Danish descent, aged 20-100 years, from the Copenhagen General Population Study, for FTO (rs9939609), MC4R (rs17782313) and TMEM18 (rs6548238), and created an allele score. A total of 10883 individuals had spirometric COPD with forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) < lower limit of normal (LLN). In these individuals, we observed 1453 exacerbations and 3390 pneumonias during 4.7 years of follow-up. For each increase in allele score, BMI was 0.28 kg/m2 [95% confidence interval (CI): 0.25-0.30) higher. Age- and sex-adjusted genetic hazard ratios (HRs) per one allele score increase in individuals with COPD were 1.13 (1.01-1.27) for exacerbations, 1.10 (1.03-1.19) for pneumonias and 1.12 (1.04-1.21) for exacerbations and/or pneumonias. Corresponding multivariable adjusted observational HRs per unit (kg/m2) BMI increase were 0.98 (0.95-1.01), 0.99 (0.96-1.03) and 0.99 (0.96-1.01), respectively. Genetically determined high BMI was associated with an increased risk of recurrent exacerbations and pneumonias in individuals with COPD, whereas this was not the case for observationally determined high BMI. The genetic data are compatible with the notion that high BMI leads to increased risk of exacerbations and pneumonias in individuals with COPD.

Combined effects of FTO rs9939609 and MC4R rs17782313 on elevated nocturnal blood pressure in the Chinese Han population.

SummaryAimIn this study we investigated the association of FTO rs9939609 and MC4R. rs17782313 with elevated blood pressure in the Chinese Han population, and analysed the relationship between the rs9939609 and rs17782313 variants.MethodsWe tested the rs9939609 and rs17782313 variants with the sequence-retrieval method.ResultsThe increase in odds ratios of the A allele of rs9939609 and the C allele of rs17782313 for nocturnal blood pressure were 1.37 and 1.69. The nocturnal blood pressure of participants simultaneously carrying the A and C alleles was significantly higher than the blood pressure of those carrying neither FTO nor MC4R risk alleles (p < 0.05), and that of the controls carrying only the A or C alleles (p < 0.05). No association between the FTO or MC4R genes with daytime hypertension was found in this Chinese population (p > 0.05).ConclusionOur data suggest that the rs9939609 and rs17782313 variants may be significantly associated with nocturnal but not daytime blood pressure levels and their combined effects were significant in this Chinese Han population.

Evaluation of the Obesity Genes FTO and MC4R for Contribution to the Risk of Large Artery Atherosclerotic Stroke in a Chinese Population

Background: Obesity is a well-established risk factor for large artery atherosclerotic (LAA) stroke. The aim of the study was to explore whether obesity genes, such as MC4R and FTO, contribute to LAA stroke risk in the Chinese Han population. Methods: 322 LAA stroke patients and 473 controls were recruited. Gene polymorphism of MC4R (rs17782313) and FTO (rs8050136 and rs9939609) were genotyped. Results: No differences were observed in genotype frequencies of variants of FTO (rs8050136 and rs9939609) or MC4R (rs17782313) between LAA stroke patients and control subjects. However, rs17782313 of the MC4R gene was associated with LAA stroke susceptibility in smokers (rs17782313: p = 0.020, OR (95% CI) = 1.55 (1.07-2.23)) in the stratified analysis. Furthermore, multifactor dimensionality reduction analysis revealed that the combination of MC4R variant (rs17782313), hypertension and smoking habit was significantly associated with increased risk of LAA stroke (p < 0.0001, OR (95% CI) = 6.57 (4.79-9.01)). Conclusion: Our study indicated that the synergistic effects of MC4R variants, hypertension, and smoking habit contribute significantly to the risk of LAA stroke in the Chinese Han population. The finding revealed that obesity gene MC4R contribute to the risk of LAA stroke via a synergistic mechanism, which will provide new insight into the genetic architecture of LAA stroke.

Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey

IntroductionPlacental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression. MethodsSouthampton Women's Survey children (n = 1990) with measurements of fetal growth from 11 to 34 weeks gestation were genotyped for common gene variants in FTO (rs9939609, rs1421085) and MC4R (rs17782313). Linear mixed-effect models were used to analyse relations of gene variants with fetal growth. ResultsFetuses with the rs9939609 A:A FTO genotype had faster biparietal diameter and head circumference growth velocities between 11 and 34 weeks gestation (by 0.012 (95% CI 0.005 to 0.019) and 0.008 (0.002–0.015) standard deviations per week, respectively) compared to fetuses with the T:T FTO genotype; abdominal circumference growth velocity did not differ between genotypes. FTO genotype was not associated with placental FTO expression, but higher placental FTO expression was independently associated with larger fetal size and higher placental ASCT2, EAAT2 and y + LAT2 amino acid transporter expression. Findings were similar for FTO rs1421085, and the MC4R gene variant was associated with the fetal growth velocity of head circumference. DiscussionFTO gene variants are known to associate with obesity but this is the first time that the risk alleles and placental FTO expression have been linked with fetal growth trajectories. The lack of an association between FTO genotype and placental FTO expression adds to emerging evidence of complex biology underlying the association between FTO genotype and obesity.

Melanocortin-4 Receptor Gene Variation Is Associated with Eating Behavior in Chilean Adults

Background/Aims: To evaluate the association between allelic variants of melanocortin receptors -3 and -4 (MC3R and MC4R, respectively) and leptin receptor (LEPR) genes with body mass index (BMI) and eating behavior. Methods: We selected 344 Chilean adults (57.8% women; age 39.1 ± 6.6 years) with a wide variation in BMI (30.3 ± 6.3 kg/m²). The Three-Factor Eating Questionnaire-R18 that measures uncontrolled eating (UE), emotional eating (EE) and cognitive restraint scores was adapted, validated and assessed for association with BMI. Genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism techniques and Taqman assays. Results: Higher EE scores were found in obese vs. non-obese in both men (p = 0.01) and women (p < 0.001). UE scores were significantly associated with BMI only in women (p = 0.002). No significant differences in eating behavior scores or BMI were found by LEPR (rs1137101, rs8179183 and rs1137100 polymorphisms) or MC3R (rs3746619 and rs3827103). Carriers of the C allele for MC4R rs17782313 showed significantly higher scores of UE compared to non-carriers (2.3 ± 0.8 vs. 2.0 ± 0.7; p = 0.02). Additionally, we also report a monogenic case of obesity carrying the pathogenic mutation 449C>T (Thr150Ile) in MC4R gene with no apparent alterations in eating behavior scores. Conclusions: UE scores were higher in C-allele carriers of MC4R-rs17782313 compared to non-carriers.

APPROACHES TO THE LIPID METABOLISM GENES POLYMORPHYSM ANALYSIS IN SCREENING FOR ATHEROSCLEROSIS RISK FACTORS

The review concerns he etiology of polygenic hyperlipidemias. The most prominent and prevalent in more than 1% of inhabitants genetic markers are discussed. The mechanisms of minor alleles influence on the hypercholesterolemia are shown: APOAI 75G>A (rs670), CETP (rs5882), LIPC (rs1800588), APOE (E2/E3/E4), hypertrigliceridemia: APOA5 (rs3135506), FABP2 rs1799883, LPL rs328. Also the genetic markers discussed that influence food-seeking behavior and by various ways do increase daily fat intake: CD36 (rs1761667), FTO (rs8050136), MC4R (rs17782313). Carrying of several pathologic alleles in a patients does significantly increase the risk of primary hyperlipidemias. More studies needed to evaluate the effect of different genetic markers combination to invent these tests as an instrument of personified predictive medicine in clinical practice.

Obese individuals experience wheezing without asthma but not asthma without wheezing: a Mendelian randomisation study of 85 437 adults from the Copenhagen General Population Study

BackgroundObservational studies suggest that obesity is associated with increased risk of asthma. However, it is unknown whether this could be explained by wheezing. We tested the hypothesis that high body...

A common variant near BDNF is associated with dietary calcium intake in adolescents

Specific targets for most obesity candidate genes discovered by genomewide association studies remain unknown. Such genes are often highly expressed in the hypothalamus, indicating their role in energy homeostasis. We aimed to evaluate the associations of selected gene variants with adiposity and dietary traits. Anthropometric parameters, fat mass, dietary intake (total energy, fat, protein, carbohydrate, fiber, and calcium) and 10 gene variants (in/near TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R and FTO) were analyzed in 1953 Czech individuals aged 10.0 to 18.0 years (1035 nonoverweight and 918 overweight: body mass index [BMI] ≥90th percentile). Obesity risk alleles of TMEM18 rs7561317, SEC16B rs10913469, and FTO rs9939609 were related to increased body weight and BMI (P < .005). The FTO variant also showed a significant positive association with waist circumference and fat mass (P < .001). Overweight adolescents had a lower total energy intake (P < .001) but a higher percentage of fat (P = .009) and protein intake (P < .001) than the nonoverweight subjects. There was also a lower calcium intake in the overweight group (P < .001). An association with at least one component of dietary intake was found in 3 of 10 studied gene variants. The MC4R rs17782313 was associated negatively with protein (P = .012) and positively associated with fiber (P = .032) intakes. The obesity risk alleles of BDNF rs925946 and FTO rs9939609 were related to a lower calcium intake (P = .001 and .037). The effects of FTO and MC4R variants, however, disappeared after corrections for multiple testing. Our results suggest that the common BDNF variant may influence dietary calcium intake independent of BMI.

Interaction between common variants of FTO and MC4R is associated with risk of PCOS.

BackgroundPolycystic ovary syndrome (PCOS) is a common and complex endocrine-metabolic disease. One of the well-documented characteristics of PCOS is obesity or overweightness. It is possible to be genetically predisposed to becoming obese or overweight, and several potentially causative single nucleotide polymorphisms (SNPs), such as rs9939609 (A/T) in the fat mass, and obesity-associated gene (FTO) and rs17782313 (T/C) in the melanocortin-4 receptor gene (MC4R), have been investigated. Further investigation of association between obesity-associated SNPs and PCOS susceptibility will contribute to a better understanding of the disease.MethodsIn the present study, we enrolled 733 patients with PCOS and 892 control subjects. The common variants FTO rs9939609 and MC4R rs17782313 were genotyped and their relationship with obesity-related traits was evaluated.ResultsRs9939609 and rs17782313 are associated with PCOS and obesity-related traits and profiles. The association found between PCOS and FTO rs9939609 (p = 0.0302) was attenuated after adjustment for BMI (p = 0.187). MC4R rs17782313 did not confer an increased risk for PCOS (p = 0.368) even after adjustments (p = 0.715). Interestingly, the interaction of FTO and MC4R polymorphisms was more significantly associated with PCOS (p = 0.031, adjusted for age and BMI). The FTO variant rs9939609 is associated with Chinese women with PCOS; however, this association is affected by BMI.ConclusionsThe combined pathogenic effect of FTO and MC4R polymorphisms indicates a direct role of the interaction between FTO and MC4R polymorphisms in the development of PCOS.

Associations between a common variant near the MC4R gene and serum triglyceride levels in an obese pediatric cohort.

Polymorphisms near the MC4R gene may be related to an increased risk for obesity, but studies of variations in this gene and its relation to cardiometabolic profiles and food intake are scarce and controversial. The aim of this study is to evaluate the influence of the variants rs12970134 and rs17782313 near the MC4R gene in food intake, binge eating (BE) behavior, anthropometric parameters, body composition, metabolic profile, and cardiometabolic risk factors in obese children and adolescents. This is a cross-sectional study that included obese children and adolescents. We evaluated anthropometric, metabolic parameters and cardiometabolic risk factors, including hypertension, impaired fasting glucose, hypertriglyceridemia, and low HDL-cholesterol. BE was assessed through the BE scale, and a 24-h recall was used to evaluate total caloric intake and percentage of macronutrients and types of dietary fat. The MC4R variants rs12970134 and rs17782313 were genotyped using TaqMan assay. To assess the magnitude of risk, a logistic regression adjusted for Z-BMI, age, and gender was performed, adopting the significance level of 0.05. The study included 518 subjects (52.1 % girls, 12.7 ± 2.7 years old, Z-BMI = 3.24 ± 0.57). Carriers of the variant rs17782313 exhibit increased triglyceride levels (108 ± 48 vs. 119 ± 54, p = 0.034) and an increased risk of hypertriglyceridemia (OR 1.985, 95 % CI 1.288-3.057, p = 0.002). There was no association of the SNP rs12970134 with clinical, metabolic, or nutritional parameters. The variant rs12970134 and rs17782313 did not influence food intake or the presence of BE. The variant rs17782313 is associated with an increased risk of hypertriglyceridemia in obese children and adolescents.