scholarly journals Functional Single-Nucleotide Polymorphisms in the Secretogranin III (SCG3) Gene that Form Secretory Granules with Appetite-Related Neuropeptides Are Associated with Obesity

2007 ◽  
Vol 92 (3) ◽  
pp. 1145-1154 ◽  
Author(s):  
Atsushi Tanabe ◽  
Takahiro Yanagiya ◽  
Aritoshi Iida ◽  
Susumu Saito ◽  
Akihiro Sekine ◽  
...  

Abstract Context: Genetic factors are important for the development of obesity. However, the genetic background of obesity still remains unclear. Objective: Our objective was to search for obesity-related genes using a large number of gene-based single-nucleotide polymorphisms (SNPs). Design and Setting: We conducted case-control association analyses using 94 obese patients and 658 controls with 62,663 SNPs selected from the SNP database. SNPs that possessed P ≤ 0.02 were further analyzed using 796 obese and 711 control subjects. One SNP (rs3764220) in the secretogranin III (SCG3) gene showed the lowest P value (P = 0.0000019). We sequenced an approximately 300-kb genomic region around rs3764220 and discovered SNPs for haplotype analyses. SCG3 was the only gene within a haplotype block that contained rs3764220. The functions of SCG3 were studied. Patients: Obese subjects (body mass index ≥ 30 kg/m2, n = 890) and control subjects (general population; n = 658, body mass index ≤ 25kg/m2; n = 711) were recruited for this study. Results: Twelve SNPs in the SCG3 gene including rs3764220 were in almost complete linkage disequilibrium and significantly associated with an obesity phenotype. Two SNPs (rs16964465, rs16964476) affected the transcriptional activity of SCG3, and subjects with the minor allele seemed to be resistant to obesity (odds ratio, 9.23; 95% confidence interval, 2.77–30.80; χ2 = 19.2; P = 0.0000067). SCG3 mRNA and immunoreactivity were detected in the paraventricular nucleus, lateral hypothalamic area, and arcuate nucleus, and the protein coexisted with orexin, melanin-concentrating hormone, neuropeptide Y, and proopiomelanocortin. SCG3 formed a granule-like structure together with these neuropeptides. Conclusions: Genetic variations in the SCG3 gene may influence the risk of obesity through possible regulation of hypothalamic neuropeptide secretion.

2019 ◽  
Vol 55 (10) ◽  
pp. 1282-1293
Author(s):  
E. A. Trifonova ◽  
A. A. Popovich ◽  
K. V. Vagaitseva ◽  
A. V. Bocharova ◽  
M. M. Gavrilenko ◽  
...  

BioFactors ◽  
2013 ◽  
Vol 39 (3) ◽  
pp. 315-325 ◽  
Author(s):  
Rui-Xing Yin ◽  
Dong-Feng Wu ◽  
Lin Miao ◽  
Lynn Htet Htet Aung ◽  
Xiao-Li Cao ◽  
...  

2018 ◽  
Vol 18 (3) ◽  
pp. 291
Author(s):  
María D. Martínez-Martínez ◽  
Hugo Mendieta-Zerón ◽  
Luis Celis ◽  
Cristian F. Layton-Tovar ◽  
Rocío Torres-García ◽  
...  

Objectives: This study aimed to describe correlations between glucose, insulin and adipokine levels and the homeostasis model assessment (HOMA) index with regards to the presence/absence of fat mass and obesity-associated (FTO) rs9939609 and peroxisome proliferator-activated receptor (PPAR)-y rs1801282 single nucleotide polymorphisms (SNPs) as indicators of body mass index in adolescents. Methods: This cross-sectional study was conducted between September and December 2016 in Toluca, Mexico. A total of 71 students between 14–18 years old were included. Various anthropometric and laboratory measurements were collected, including lipid profile, glucose, insulin and adipokine levels and HOMA index. The degree of association between variables was evaluated with regards to the presence/absence of the SNPs. Results: Leptin levels were significantly higher among female students (P = 0.001), although adiponectin levels did not differ significantly (P = 0.060). There were significant positive correlations between insulin levels and HOMA index with FTO (r = 0.391; P = 0.007 and r = 0.413; P = 0.005, respectively) and PPARγ (r = 0.529; P = 0.007 and r = 0.537; P = 0.007, respectively) SNPs. Leptin showed a significant positive correlation in the presence of PPARγ (r = 0.483; P = 0.007) or in the absence of both SNPs (r = 0.627; P = 0.039). However, adiponectin was significantly negatively correlated in the presence of FTO, either alone (r = −0.333; P = 0.024) or in combination with PPARγ (r = −0.616; P = 0.043). Conclusion: The presence of FTO and/or PPARγ SNPs might be related to a genetic predisposition to metabolic syndrome.Keywords: Obesity; Body Mass Index; Single Nucleotide Polymorphisms; Fat Mass and Obesity Associated Protein, Human; Peroxisome Proliferator-Activated Receptor gamma; Adipokines.


2018 ◽  
Vol 2 (S1) ◽  
pp. 36-36
Author(s):  
Ying Meng ◽  
Susan W. Groth ◽  
Joyce A. Smith ◽  
Harriet Kitzman

OBJECTIVES/SPECIFIC AIMS: The food reward circuitry regulates hedonic eating especially in relation to palatable hypercaloric foods, which can lead to chronic overeating and consequent overweight and obesity. Evidence supports that there is considerable overlap within the brain reward circuitry between palatable hypercaloric food intake and substance addiction. The goal of this study was to identify associations between addiction-related genes and body mass index. We hypothesized that addiction-related genes potentially participate in the food reward circuitry if they are associated with obesity traits. METHODS/STUDY POPULATION: A secondary analysis was conducted with 1093 African American adolescents and young adults from the New Mother’s Study. Anthropometric, genetic, demographic and lifestyle measurements were available at the 18-year follow-up assessments. A total of 1350 single nucleotide polymorphisms mapped to 127 addiction-related genes were assessed. A total of 186 ancestry informative markers were used to adjust for population stratification. Generalized estimating equation models were used to identify genetic associations, including additive, dominant, and recessive models, and control for correlations within families. RESULTS/ANTICIPATED RESULTS: The participants ranged from 15 to 23 years of age. Of them, 42.7% were overweight or obese. Significant associations with body mass index were identified for 13 single nucleotide polymorphisms mapped to 11 addiction-related genes, including LEP (p 0.027–<0.001). Most of these genes are involved in dopaminergic, opioidergic, serotonergic pathways, and stress. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results support the role of dopaminergic and opioidergic pathways in the food reward circuitry, and suggest a potential involvement of serotonergic pathways and genes related to stress in the food reward circuitry. Further investigation of the identified genes will facilitate delineation and understanding of the brain food reward system and its relationship with obesity.


2021 ◽  
Vol 8 (5) ◽  
pp. 53
Author(s):  
Ivana Škrlec ◽  
Jasminka Talapko ◽  
Martina Juzbašić ◽  
Robert Steiner

The growing body of evidence shows a significant difference in the circadian rhythm of cardiovascular disease based on biological sex. The incidence of cardiovascular disease varies between women and men. Additionally, biological sex is vital for the timely application of therapy—chronotherapy, which benefits both sexes. This study aimed to examine the potential difference of single nucleotide polymorphisms (SNPs) of the circadian rhythm genes ARNTL, CLOCK, CRY2 and PER2 in women and men with myocardial infarction. A cross-sectional study was conducted, including 200 patients with myocardial infarction. Altogether, ten single nucleotide polymorphisms in the ARNTL, CLOCK, CRY2 and PER2 genes were analyzed. The Chi-square test yielded statistically significant differences in CLOCK gene rs11932595 polymorphism in a recessive genotype model between women and men with a p-value of 0.03 and an odds ratio 2.66, and a corresponding 95% confidence interval of 1.07 to 6.66. Other analyzed polymorphisms of the circadian rhythm genes ARNTL, CRY2, and PER2 did not significantly differ between the sexes. According to the study’s current results, the CLOCK gene’s genetic variability might affect myocardial infarction concerning biological sex.


2021 ◽  
Vol 48 (1) ◽  
pp. 69-79
Author(s):  
Amer Mahmoud Sindiani ◽  
Osamah Batiha ◽  
Esra’a Al-zoubi ◽  
Sara Khadrawi ◽  
Ghadeer Alsoukhni ◽  
...  

Objective: Poor ovarian response (POR) refers to a subnormal follicular response that leads to a decrease in the quality and quantity of the eggs retrieved after ovarian stimulation during assisted reproductive treatment (ART). The present study investigated the associations of multiple variants of the estrogen receptor 2 (ESR2) and follicle-stimulating hormone receptor (FSHR) genes with POR in infertile Jordanian women undergoing ART.Methods: Four polymorphisms, namely ESR2 rs1256049, ESR2 rs4986938, FSHR rs6165, and FSHR rs6166, were investigated in 60 infertile Jordanian women undergoing ART (the case group) and 60 age-matched fertile women (the control group), with a mean age of 33.60±6.34 years. Single-nucleotide polymorphisms (SNPs) were detected by restriction fragment length polymorphism and then validated using Sanger sequencing.Results: The p-value of the difference between the case and control groups regarding FSHR rs6166 was very close to 0.05 (p=0.054). However, no significant differences were observed between the two groups in terms of the other three SNPs, namely ESR2 rs1256049, ESR2 rs4986938, and FSHR rs6165 (p=0.561, p=0.433, and p=0.696, respectively).Conclusion: The association between FSHR rs6166 and POR was not statistically meaningful in the present study, but the near-significant result of this experiment suggests that statistical significance might be found in a future study with a larger number of patients.


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