Evaluation of MC4R [RS17782313, RS17700633], AGRP [RS3412352] and POMC [RS1042571] polymorphisms with obesity in Northern India
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SUBMITTER: Srivastava A
PROVIDER: S-EPMC4044147 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectiveGenetic variants of the melanocortin-4 receptor gene (MC4R), agouti related protein (AGRP) and proopiomelanocortin (POMC) are reported to be associated with obesity. Therefore, the aim of this study is to examine MC4R rs17782313, MC4R rs17700633, AGRP rs3412352 and POMCrs1042571 for any association with obesity in North Indian subjects.MethodsThe variants were investigated for association in 300 individuals with BMI ≥30 kg/m(2) and 300 healthy non-obese individuals BMI <30 kg/m(2.) The genotyping were analyzed by Taqman probes. The statistical analysis was performed by the SPSS software, ver.19 and p≤0.05 was considered statistically significant.ResultsThe genotypes of MC4R rs17782313 and POMC rs1042571 were significantly associated with obesity (C), (p=0.02; OR=1.7 and p=0.01; OR=1.6, respectively); however, MC4Rrs17700633 (p=0.001; OR=0.55) was associated with low risk. In addition, AGRPrs3412352 (p=0.93; OR=0.96) showed no association with obesity (BMI ≥30 kg/m(2)) in North Indian subjects.ConclusionThis study provides the report about the significant association of MC4R (rs17782313) and POMC (rs1042571) with morbid obesity (BMI ≥30 kg/m(2)), but MC4R (rs17700633) and AGRP (rs34123523) did not show any association with obesity in the studied North Indian population.
| S-EPMC3976726 | biostudies-literature
Project description:ObjectivesObesity is a significant risk factor for a number of chronic diseases, including diabetes, cardiovascular diseases, and cancer. Obesity usually results from a combination of causes and contributing factors, including genetics and lifestyle choices. Many studies have shown an association of single nucleotide polymorphisms (SNPs) in the fat mass and obesity-associated (FTO) and the melanocortin-4 receptor (MC4R) genes with body mass index (BMI). Therefore, recognizing the main genes and their relevant genetic variants will aid prediction of obesity risk. The aim of our study was to investigate the frequency of rs9939609 and rs17782313 polymorphisms in FTO and MC4R genes in an Iranian population.MethodsWe enrolled 130 obese patients and 83 healthy weight controls and calculated their BMI. Genomic DNA was extracted from peripheral blood and the frequency of rs9939609 and rs17782313 polymorphisms in FTO and MC4R genes was determined using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR).ResultsSignificant associations were found between FTO rs9939609 and BMI. Where homozygous risk allele carriers (A-A) have significant higher odds ratio (OR) of being obese than individuals with normal BMI (OR = 6.927, p < 0.005, 95% confidence interval (CI): 3.48-13.78). No significant correlation between MC4R rs17782313 and obesity were observed when compared to healthy weight individuals. Although subjects with C-C genotype had higher odds of obesity (OR = 1.889, p = 0.077, 95%CI: 0.92-3.84).ConclusionsThis study shows a relationship between FTO polymorphism and increased BMI, therefore, SNP in the FTO gene influence changes in BMI and can be considered a prognostic marker of obesity risk.
| S-EPMC6330185 | biostudies-literature
Project description:Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p?=?0.001 and p?=?0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR) ?=?1.17; 95% confidence interval (CI): 1.03-1.32, p?=?0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR?=?0.98; 95% CI: 0.91-1.06; p?=?0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.
| S-EPMC3035652 | biostudies-literature
Project description:Obesity is a multifactorial disease whose onset and development are shaped by the individual genetic background. The melanocortin 4 receptor gene (MC4R) is involved in the regulation of food intake and energy expenditure. Some of the single nucleotide polymorphisms (SNPs) of this gene are related to obesity and metabolic risk factors. The present study was undertaken to assess the relationship between three polymorphism SNPs, namely, rs17782313, rs17773430 and rs34114122, and obesity and metabolic risk factors. One hundred seventy-eight children with obesity aged between 7 and 16 years were studied to determine anthropometric variables and biochemical and inflammatory parameters. Our results highlight that metabolic risk factors, especially alterations in carbohydrate metabolism, were related to rs17782313. The presence of the minor C allele in the three variants (C-C-C) was significantly associated with anthropometric measures indicative of obesity, such as the body mass and fat mass indexes, and increased the values of insulinemia to 21.91 µIU/mL with respect to the wild type values. Our study suggests that the C-C-C haplotype of the SNPs rs17782313, rs17773430 and rs34114122 of the MC4R gene potentiates metabolic risk factors at early ages in children with obesity.
| S-EPMC10378299 | biostudies-literature
Project description:Background/objectivesMelanocortins have a crucial role in appetite and weight regulation. Although the melanocortin 4 receptor (MC4R) gene has been repeatedly linked to obesity and antipsychotic-induced weight gain, the mechanism behind how it leads to this effect in still undetermined. The goal of this study was to conduct an in-depth and sophisticated analysis of MC4R polymorphisms, body mass index (BMI), eating behavior and depressed mood.Subjects/methodsWe genotyped 328 individuals of European ancestry on the following MC4R markers based on the relevant literature on obesity and antipsychotic-induced weight gain: rs571312, rs17782313, rs489693, rs11872992, and rs8087522. Height and weight were measured, and information on depressed mood and overeating behaviors was obtained during the in-person assessment.ResultsBMI was associated with rs17782313 C allele; however, this finding did not survive correction for multiple testing (P = 0.018). Although rs17782313 was significantly associated with depressed mood and overeating behaviors, tests of indirect effects indicated that emotional eating and food cravings, rather than depressed mood, uniquely accounted for the effect of this marker and BMI (n = 152).ConclusionsTo our knowledge, this is the first study to investigate the link between MC4R rs17782313, mood and overeating behavior, as well as to demonstrate possible mechanisms behind MC4R's influence on body weight. If replicated in a larger sample, these results may have important clinical implications, including potential for the use of MC4R agonists in the treatment of obesity and disordered eating.
| S-EPMC4232480 | biostudies-literature
Project description:Melanocortin-4 receptor (MC4R) has been reported to be associated with the risk of obesity, and metabolically unhealthy obese (MUHO) patients tend to have a greater risk of cardiovascular complications than metabolically healthy obese (MHO) patients. Therefore, we aimed to study single nucleotide polymorphisms (SNPs) in the MC4R gene associated with metabolically healthy and unhealthy obesity in Chinese Northern Han populations. A total of 1100 Chinese Northern Han subjects were recruited and divided into four groups according to the criteria of the Adult Treatment Panel-III (ATP-III) and World Health Organization (WHO): MUHO (n = 300), MHO (n = 196), metabolic unhealthy normal weight (MUH-NW) (n = 303), and metabolic healthy normal weight (MH-NW) (n = 301). DNA samples were extracted, and six SNPs of the MC4R gene, including rs2331841, rs656710, rs17782313, rs571312, rs12970134, and rs11872992, were genotyped with the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. Among the six SNPs of the MC4R gene, rs2331841 (A/G) was the most significant and could account for 0.9% of obesity etiology. Compared with the normal weight group, rs2331841 of the MC4R gene was associated with obesity (P=0.032). The obesity risk of subjects with the AG genotype in the rs2331841 site was 82% higher than the risk of those with the GG genotype (β = 0.60, OR = 1.82, P=0.030). After adjusting for sex and age, the frequency of the A allele in the rs2331841 site was higher in the MUHO group than in the MH-NW group (27.9% vs. 21.1%, respectively, OR = 1.49, 95% CI 1.14-1.96, P=0.005) and in the MUHO group than in the MHO group (27.9% vs. 22.3%, respectively, OR = 1.39, 95% CI 1.02-1.92, P=0.039). Among the three genotypes of rs2331841, the subjects with the AA/AG genotype had higher diastolic blood pressure (DBP) than those with the GG genotype. Our data first suggest that SNPs in the rs2331841 site of the MC4R gene are closely related to obesity and its related metabolic disorders in Chinese Northern Han populations. The participants with an A allele of rs2331841 had a higher risk of obesity and MUHO than other participants.
| S-EPMC6875380 | biostudies-literature
Project description:Earlier GWAS has identified that rs17782313 near MC4R was associated with obesity. However, subsequent studies showed conflicting results, especially among childhood. Besides, the mechanisms underlying the association between rs17782313 and childhood obesity remain largely unexplored, and genetic and epigenetic may interact and together affect the development of childhood obesity. We conducted a comprehensive meta-analysis to assess the association between rs17782313 and childhood obesity. MeQTL and eQTL analysis was applied to explore the effect of rs17782313 on DNA methylation and MC4R expression. We found that rs17782313 near MC4R was associated with increased childhood obesity risk and BMI z-score in several inheritable models (P < 0.05). Additionally, the similar trend was observed among subgroups of Asians, Caucasian. Furthermore, meQTL and eQTL analysis indicated that individuals carrying rs17782313 TT genotype were significantly associated with increased methylation level of cg10097150 located in MC4R promoter and decreased expression of MC4R than those with CT/CC genotype (P = 1.7 × 10-4 and P = 1.9 × 10-3 respectively). Our results strongly confirmed that rs17782313 was associated with increased risk of childhood obesity. Furthermore, rs17782313 T allele was correlated with promoter hypermethylation and decreased expression of MC4R, thus involved in the development of childhood obesity.
| S-EPMC5356842 | biostudies-literature
Project description:Activation of melanocortin-4 receptor (MC4R) by insulin sensitive neurons is a central mechanism in body weight regulation, and genetic variants in the MC4R gene (e.g., rs17782313) are associated with obesity. By using magnetoencephalography, we addressed whether rs17782313 affects the cerebrocortical insulin response. We measured the cerebrocortical insulin response by using magnetoencephalography in a hyperinsulinemic euglycemic clamp (versus placebo) in 51 nondiabetic humans (26 f/25 m, age 35 ± 3 years, BMI 28 ± 1?kg/m(2)). The C-allele of rs17782313 was minor allele (frequency 23%), and the genotype distribution (TT 30, TC 19, CC 2) was in Hardy-Weinberg-Equilibrium. Insulin-stimulated cerebrocortical theta activity was decreased in the presence of the C-allele (TT 33 ± 16?fT; TC/CC -27 ± 20?fT; P = .023), and this effect remained significant after adjusting for BMI and peripheral insulin sensitivity (P = .047). Cerebrocortical theta activity was impaired in carriers of the obesity risk allele. Therefore, cerebral insulin resistance may contribute to the obesity effect of rs17782313.
| S-EPMC3136179 | biostudies-literature
Project description:The global rise in obesity is attributed to genetic predisposition interaction with an obesogenic environment. Melanocortin 4 receptor (MC4R) rs17782313 polymorphism has been linked to common obesity with varying influence across different populations. MC4R is a crucial player in the leptin proopiomelanocortin pathway that regulates weight hemostasis. We aimed to study MC4R rs17782313 and its interaction with eating behaviors on obesity predisposition in the Israeli population. Adults' (n = 5785, >18 y) genotype and anthropometric and demographic data were analyzed using logistic regression models adjusting for age, sex, T1DM, and T2DM. MC4R rs17782313 significantly predisposes to elevated obesity risk under the recessive and additive models (OR = 1.38, 95% CI: 1.1-1.72, p = 0.005 and OR = 1.1, 95% CI: 1.01-1.2, p = 0.03, respectively) adjusted for confounders (age, sex, T1DM, and T2DM). Stratification by sex demonstrated that carrying the common MC4R rs17782313 is significantly associated with an elevated predisposition to obesity under the recessive model among females only (OR = 1.41, 95% CI: 1.09-1.82, p = 0.01), with an average of 0.85 BMI increment compared with wild type and one risk allele carriers. MC4R rs17782313 significantly interacted with several eating behaviors to enhance the risk of obesity. Our findings demonstrate that MC4R rs17782313 homozygous female carriers are significantly predisposed to obesity amplified by eating behaviors.
| S-EPMC10671328 | biostudies-literature
Project description:MC4R represents a key player involved in melanocortin-mediated control of energy balance. Recently identified near MC4R variant rs17782313 (T > C) can serve as a contributing factor for obese phenotype but its association with obesity has never been sought in a sample of the Pakistani population. The role of genetic variants as causal factors varies across populations. Association studies in a specific population can help us to distinguish global from local gene-gene and gene-environment interactions. This is the first study that investigated the association of rs17782313 with obesity and various obesity-linked anthropometric, metabolic, physical, and behavioural traits in Pakistani subjects including 306 OW/OB (overweight and obese) and 300 NW (normal weight) individuals. The comparison of various aforementioned obesity-linked continuous and categorical variables between OW/OB and NW subjects revealed that almost all variables were found significantly aberrant (p < 0.05) in OW/OB subjects as compared to their age- and gender-matched NW controls indicating greater risk of developing various cardio-metabolic disorders. The genotyping of rs17782313 showed significant association of this variant with obesity and obesity-linked anthropometric traits in females suggesting the gender-specific effect of this variant in our population. The minor allele C increased the risk of obesity by 1.55 times (95% CI = 1.1-2.18, p = 0.01) whereas homozygous CC genotype increased the risk by 2.43 times (95% CI = 1.19-4.96, p = 0.015) in females. However, no association of rs17782313 was observed with any of the obesity-linked metabolic, physical, and behavioural traits except random eating timings. In conclusion, the current study significantly contributes to the knowledge of the genetic proneness to obesity in Pakistani females. This could also be helpful for forthcoming meta-analysis studies elucidating which variants are truly associated with the susceptibility to develop an obese phenotype.
| S-EPMC9080305 | biostudies-literature