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 < or = 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 > or = 30 kg/m(2), n = 890) and control subjects (general population; n = 658, body mass index < or = 25 kg/m(2); 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; chi(2) = 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.
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 obesepatients and 658 controls with 62,663 SNPs selected from the SNP database. SNPs that possessed P < or = 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 > or = 30 kg/m(2), n = 890) and control subjects (general population; n = 658, body mass index < or = 25 kg/m(2); 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; chi(2) = 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.
Authors: Reza Pourhaghighi; Peter E A Ash; Sadhna Phanse; Florian Goebels; Lucas Z M Hu; Siwei Chen; Yingying Zhang; Shayne D Wierbowski; Samantha Boudeau; Mohamed T Moutaoufik; Ramy H Malty; Edyta Malolepsza; Kalliopi Tsafou; Aparna Nathan; Graham Cromar; Hongbo Guo; Ali Al Abdullatif; Daniel J Apicco; Lindsay A Becker; Aaron D Gitler; Stefan M Pulst; Ahmed Youssef; Ryan Hekman; Pierre C Havugimana; Carl A White; Benjamin C Blum; Antonia Ratti; Camron D Bryant; John Parkinson; Kasper Lage; Mohan Babu; Haiyuan Yu; Gary D Bader; Benjamin Wolozin; Andrew Emili Journal: Cell Syst Date: 2020-04-22 Impact factor: 10.304
Authors: Alessandro Bartolomucci; Roberta Possenti; Sushil K Mahata; Reiner Fischer-Colbrie; Y Peng Loh; Stephen R J Salton Journal: Endocr Rev Date: 2011-08-23 Impact factor: 19.871
Authors: Claire Monnereau; Pauline W Jansen; Henning Tiemeier; Vincent W V Jaddoe; Janine F Felix Journal: Obesity (Silver Spring) Date: 2017-02-28 Impact factor: 5.002
Authors: Eivind Larssen; Cato Brede; Anne Hjelle; Anne Bolette Tjensvoll; Katrine Brække Norheim; Kjetil Bårdsen; Kristin Jonsdottir; Peter Ruoff; Roald Omdal; Mari Mæland Nilsen Journal: SAGE Open Med Date: 2019-05-13