MC4R and ENPP1 gene polymorphisms and their implication in maternal and neonatal risk for obesity.
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ABSTRACT:
SUBMITTER: Marginean C
PROVIDER: S-EPMC6659701 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
MC4R and ENPP1 gene polymorphisms and their implication in maternal and neonatal risk for obesity.
Mărginean Claudiu C Mărginean Cristina Oana CO Iancu Mihaela M Meliț Lorena Elena LE Tripon Florin F Bănescu Claudia C
Scientific reports 20190726 1
The aims of this study were to establish the role of MC4Rrs17782313 and ENPP1rs1044498 gene polymorphisms on pre-pregnancy BMI and the newborn's status. We performed a cross-sectional study on 185 mothers and their offspring. The groups were divided into: control group- underweight or normal mothers with BMI<sub>initial</sub> < 25 kg/m<sup>2</sup> (n<sub>1</sub> = 134) and study group-overweight/obese mothers with BMI<sub>initial</sub> ≥ 25 kg/m<sup>2</sup> (n<sub>2</sub> = 51). All subjects und ...[more]
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Project description:BackgroundRecent genome wide association studies (GWAS) and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms (SNPs) associated with obesity, mostly in Europeans. We aimed to assess the contribution of some of these SNPs to obesity risk and to the variation of related metabolic traits, in Mexican children.MethodsThe association of six European obesity-related SNPs in or near FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes with risk of obesity was tested in 1,463 school-aged Mexican children (N(cases) = 514; N(controls) = 949). We also assessed effects of these SNPs on the variation of body mass index (BMI), fasting serum insulin levels, fasting plasma glucose levels, total cholesterol and triglyceride levels, in a subset of 1,171 nonobese Mexican children.ResultsWe found a significant effect of GNPDA2 rs10938397 on risk of obesity (odds ratio [OR] = 1.30; P = 1.34 × 10-3). Furthermore, we found nominal associations between obesity risk or BMI variation and the following SNPs: ENPP1 rs7754561, MC4R rs17782313 and NEGR1 rs2815752. Importantly, the at-risk alleles of both MC4R rs17782313 and NPC1 rs1805081 showed significant effect on increased fasting glucose levels (β = 0.36 mmol/L; P = 1.47 × 10(-3)) and decreased fasting serum insulin levels (β = -0.10 μU/mL; P = 1.21 × 10(-3)), respectively.ConclusionOur present results suggest that some obesity-associated SNPs previously reported in Europeans also associate with risk of obesity, or metabolic quantitative traits, in Mexican children. Importantly, we found new associations between MC4R and fasting glucose levels, and between NPC1 and fasting insulin levels.
| S-EPMC3577489 | biostudies-literature
Project description:BackgroundLittle is known about the correlation between the melanocortin 4 receptor gene (MC4R) single nucleotide polymorphisms (SNPs) and the risk of obesity. This research sought to test the MC4R rs17782313, rs476828 and rs12970134 SNPs, their haplotypes and gene-environment interactions on the risk of obesity in the Maonan ethnic group, an isolated minority in China.MethodsA case-control study comprised of 1836 participants (obesity group, 858; and control group, 978) was conducted. Genotypes of the three SNPs were determined by the next-generation sequencing (NGS) technology.ResultsThe genotypic frequencies of the three SNPs were different between the obesity and control groups (P < 0.05 for all). The minor allelic frequency of the MC4R rs17782313C, rs476828C and rs12970134A was higher in obesity than in control groups (13.8% vs. 8.3%, P < 0.001, 17.1% vs. 10.9%, P < 0.001; and 15.5% vs. 11.5%, P < 0.001; respectively). Additionally, the dominant model of rs17782313 and rs476828 SNPs revealed an increased morbidity function on the risk of obesity (P < 0.05). A correlation between SNP-environment and the risk of obesity was also observed. The rs17782313C-rs476828C-rs12970134A haplotype was associated with high risk of obesity (OR = 1.796, 95% CI = 1.447-2.229), whereas the rs17782313T-rs476828T-rs12970134G and rs17782313T-rs476828T-rs12970134A haplotypes were associated with low risk of obesity (OR = 0.699, 95% CI = 0.586-0.834 and OR = 0.620, 95% CI = 0.416-0.925; respectively). The interactions between haplotype and waist circumference on the risk of obesity were also noted.ConclusionsWe discovered that the MC4R rs17782313, rs476828 and rs12970134 SNPs and their haplotypes were associated with the risk of obesity in the Chinese Maonan population.
| S-EPMC7414557 | biostudies-literature
Project description:OBJECTIVES:To determine (1) whether higher maternal body mass index (BMI) and Cesarean (C) Section mode of delivery are associated with neonatal hypoglycemia (NH) and (2) whether timing of NH onset differs by risk factors. STUDY DESIGN:Retrospective cohort study (n?=?4602) to determine the odds of NH, NH requiring IV dextrose and timing of NH onset among infants with established and plausible (BMI and C-section) risk factors. RESULT:Infants born to class III obese mothers had higher odds of NH (OR 1.3, 95% CI 1.0-1.8) and of requiring IV dextrose (OR 2.2, 95% CI 1.2-3.9). Infants born via C-section had higher odds of requiring IV dextrose (OR 1.4, 95% CI 1.1-1.9). Infants who were delivered to high BMI mothers and by C-section developed NH earlier than the reference group. CONCLUSION:Determining the predictors and timing of NH onset may help develop tailored evaluation and management strategies for at-risk neonates.
| S-EPMC6660417 | 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 in pregnancy may negatively influence maternal and infant iron status. The aim of this study was to examine the association of obesity with inflammatory and iron status in both mother and infant in two prospective studies in pregnancy: UPBEAT and SCOPE. Maternal blood samples from obese (n = 245, BMI ? 30 kg/m²) and normal weight (n = 245, BMI < 25 kg/m²) age matched pregnant women collected at approximately 15 weeks' gestation, and umbilical cord blood samples collected at delivery, were analysed for a range of inflammatory and iron status biomarkers. Concentrations of C- reactive protein and Interleukin-6 in obese women compared to normal weight women were indicative of an inflammatory response. Soluble transferrin receptor (sTfR) concentration [18.37 nmol/L (SD 5.65) vs 13.15 nmol/L (SD 2.33)] and the ratio of sTfR and serum ferritin [1.03 (SD 0.56) vs 0.69 (SD 0.23)] were significantly higher in obese women compared to normal weight women (P < 0.001). Women from ethnic minority groups (n = 64) had higher sTfR concentration compared with white women. There was no difference in maternal hepcidin between obese and normal weight women. Iron status determined by cord ferritin was not statistically different in neonates born to obese women compared with neonates born to normal weight women when adjusted for potential confounding variables. Obesity is negatively associated with markers of maternal iron status, with ethnic minority women having poorer iron statuses than white women.
| S-EPMC6115715 | biostudies-literature
Project description:IntroductionObesity plays a pivotal role in the development of metabolic syndrome-excessive body fat, spikes in blood glucose levels and hypertension-and ultimately leads to cardiovascular diseases and type 2 diabetes (T2D), if left unattended. The present study aimed to investigate the associated risk of T2D with obesity risk alleles of fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes.MethodsThe study includes 400 subjects (300 T2D diabetic cases and 100 healthy controls). Genetic analysis was done by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.ResultsThe findings of the study show no significant increase in odds of diabetes associated with the prevalence of FTO and MC4R minor alleles. Rare allele frequencies for "A" of FTO rs9939609 were 0.34 and 0.30 in cases and controls, respectively. Rare allele frequencies for A of MC4R rs12970134 were found to be more common in controls (0.45) than cases (0.41), but the difference was insignificant (p 0.246); however, an increase in body weight with the presence of allele "A" of the FTO gene (p value < 0.001) was found, indicating indirect involvement in the development of T2D. In addition, these were also correlated with the demographic/lifestyle and clinico-pathological parameters between T2D cases and controls. We found that T2D patients with a history of smoking and high consumption of alcohol, fast foods and sweetened beverages are at high risk of T2D compared to healthy controls (p < 0.01*).ConclusionThe present study concludes that there is no direct association of rs9939609 of the FTO gene with the occurrence of diabetes in the Indian population, but its role in T2D development cannot be overlooked altogether. Furthermore, we conclude that the rs9939609 of FTO carries a potential risk of obesity and because of this FTO rs9939609 T > A is widely considered an obesity-associated allele/single-nucleotide polymorphism (SNP).
| S-EPMC7395207 | 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:BackgroundGenome-wide association studies on Europeans have shown that two polymorphisms (rs17782313, rs12970134) near the melanocortin 4 receptor (MC4R) gene were associated with increased risk of obesity. Subsequently studies among different ethnic populations have shown mixed results with some confirming and others showing inconsistent results, especially among East Asians and Africans. We performed a comprehensive meta-analysis of various studies from different ethnic populations to assess the association of the MC4R polymorphism with obesity risk.MethodsWe retrieved all published literature that investigated association of MC4R variants with obesity from PubMed and Embase. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model.ResultsA total of 61 studies (80,957 cases/220,223 controls) for rs17782313 polymorphism (or proxy) were included in the meta-analysis. The results suggested that rs17782313 polymorphism was significantly associated with obesity risk (OR=1.18, 95%CI=1.15-1.21, p<0.001). Similar trends were observed among subgroups of Europeans and East Asians, adults and children, studies with high quality score, and for each five MC4R polymorphisms independently.ConclusionsThe present meta-analysis confirms the significant association of MC4R polymorphism with risk of obesity. Further studies should be conducted to identify the causal variant and the underlying mechanisms of the identified association.
| S-EPMC3458070 | biostudies-literature
Project description:BackgroundThe pathogenesis of obesity is reportedly related to variations in the fat mass and an obesity-associated gene (FTO); however, as the number of reports increases, particularly with respect to varying ethnicities, there is a need to determine more precisely the effect sizes in each ethnic group. In addition, some reports have claimed ethnic-specific associations with alternative SNPs, and to that end there has been a degree of confusion.MethodsWe searched PubMed, MEDLINE, Web of Science, EMBASE, and BIOSIS Preview to identify studies investigating the associations between the five polymorphisms and obesity risk. Individual study odds ratios (OR) and their 95% confidence intervals (CI) were estimated using per-allele comparison. Summary ORs were estimated using a random effects model.ResultsWe identified 59 eligible case-control studies in 27 articles, investigating 41,734 obesity cases and 69,837 healthy controls. Significant associations were detected between obesity risk and the five polymorphisms: rs9939609 (OR: 1.31, 95% CI: 1.26 to 1.36), rs1421085 (OR: 1.43, 95% CI: 1.33 to 1.53), rs8050136 (OR: 1.25, 95% CI: 1.13 to 1.38), rs17817449 (OR: 1.54, 95% CI: 1.41 to 1.68), and rs1121980 (OR: 1.34, 95% CI: 1.10 to 1.62). Begg's and Egger's tests provided no evidence of publication bias for the polymorphisms except rs1121980. There is evidence of higher heterogeneity, with I2 test values ranging from 38.1% to 84.5%.ConclusionsThis meta-analysis suggests that FTO may represent a low-penetrance susceptible gene for obesity risk. Individual studies with large sample size are needed to further evaluate the associations between the polymorphisms and obesity risk in various ethnic populations.
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