Functional single-nucleotide polymorphisms in the secretogranin III (SCG3) gene that form secretory granules with appetite-related neuropeptides are associated with obesity

Atsushi Tanabe, Takahiro Yanagiya, Aritoshi Iida, Susumu Saito, Akihiro Sekine, Atsushi Takahashi, Takahiro Nakamura, Tatsuhiko Tsunoda, Seika Kamohara, Yoshio Nakata, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Tohru Funahashi, Shigeru Miyazaki, Katsuto Tokunaga, Kazuyuki Hamaguchi, Tatsuo ShimadaKiyoji Tanaka, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Yuji Matsuzawa, Naoyuki Kamatani, Yusuke Nakamura, Kikuko Hotta

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1145-1154
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number3
DOIs
Publication statusPublished - Mar 2007

Fingerprint

Secretory Vesicles
Appetite
Neuropeptides
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Obesity
Genes
Lateral Hypothalamic Area
Haplotypes
Body Mass Index
Pro-Opiomelanocortin
Arcuate Nucleus of Hypothalamus
secretogranin III
Paraventricular Hypothalamic Nucleus
Neuropeptide Y
Linkage Disequilibrium
Alleles
Odds Ratio
Databases

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Functional single-nucleotide polymorphisms in the secretogranin III (SCG3) gene that form secretory granules with appetite-related neuropeptides are associated with obesity. / Tanabe, Atsushi; Yanagiya, Takahiro; Iida, Aritoshi; Saito, Susumu; Sekine, Akihiro; Takahashi, Atsushi; Nakamura, Takahiro; Tsunoda, Tatsuhiko; Kamohara, Seika; Nakata, Yoshio; Kotani, Kazuaki; Komatsu, Ryoya; Itoh, Naoto; Mineo, Ikuo; Wada, Jun; Funahashi, Tohru; Miyazaki, Shigeru; Tokunaga, Katsuto; Hamaguchi, Kazuyuki; Shimada, Tatsuo; Tanaka, Kiyoji; Yamada, Kentaro; Hanafusa, Toshiaki; Oikawa, Shinichi; Yoshimatsu, Hironobu; Sakata, Toshiie; Matsuzawa, Yuji; Kamatani, Naoyuki; Nakamura, Yusuke; Hotta, Kikuko.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 3, 03.2007, p. 1145-1154.

Research output: Contribution to journalArticle

Tanabe, A, Yanagiya, T, Iida, A, Saito, S, Sekine, A, Takahashi, A, Nakamura, T, Tsunoda, T, Kamohara, S, Nakata, Y, Kotani, K, Komatsu, R, Itoh, N, Mineo, I, Wada, J, Funahashi, T, Miyazaki, S, Tokunaga, K, Hamaguchi, K, Shimada, T, Tanaka, K, Yamada, K, Hanafusa, T, Oikawa, S, Yoshimatsu, H, Sakata, T, Matsuzawa, Y, Kamatani, N, Nakamura, Y & Hotta, K 2007, 'Functional single-nucleotide polymorphisms in the secretogranin III (SCG3) gene that form secretory granules with appetite-related neuropeptides are associated with obesity', Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 3, pp. 1145-1154. https://doi.org/10.1210/jc.2006-1808
Tanabe, Atsushi ; Yanagiya, Takahiro ; Iida, Aritoshi ; Saito, Susumu ; Sekine, Akihiro ; Takahashi, Atsushi ; Nakamura, Takahiro ; Tsunoda, Tatsuhiko ; Kamohara, Seika ; Nakata, Yoshio ; Kotani, Kazuaki ; Komatsu, Ryoya ; Itoh, Naoto ; Mineo, Ikuo ; Wada, Jun ; Funahashi, Tohru ; Miyazaki, Shigeru ; Tokunaga, Katsuto ; Hamaguchi, Kazuyuki ; Shimada, Tatsuo ; Tanaka, Kiyoji ; Yamada, Kentaro ; Hanafusa, Toshiaki ; Oikawa, Shinichi ; Yoshimatsu, Hironobu ; Sakata, Toshiie ; Matsuzawa, Yuji ; Kamatani, Naoyuki ; Nakamura, Yusuke ; Hotta, Kikuko. / Functional single-nucleotide polymorphisms in the secretogranin III (SCG3) gene that form secretory granules with appetite-related neuropeptides are associated with obesity. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 3. pp. 1145-1154.
@article{7c534f2af8154a2495963979b177387f,
title = "Functional single-nucleotide polymorphisms in the secretogranin III (SCG3) gene that form secretory granules with appetite-related neuropeptides are associated with obesity",
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.",
author = "Atsushi Tanabe and Takahiro Yanagiya and Aritoshi Iida and Susumu Saito and Akihiro Sekine and Atsushi Takahashi and Takahiro Nakamura and Tatsuhiko Tsunoda and Seika Kamohara and Yoshio Nakata and Kazuaki Kotani and Ryoya Komatsu and Naoto Itoh and Ikuo Mineo and Jun Wada and Tohru Funahashi and Shigeru Miyazaki and Katsuto Tokunaga and Kazuyuki Hamaguchi and Tatsuo Shimada and Kiyoji Tanaka and Kentaro Yamada and Toshiaki Hanafusa and Shinichi Oikawa and Hironobu Yoshimatsu and Toshiie Sakata and Yuji Matsuzawa and Naoyuki Kamatani and Yusuke Nakamura and Kikuko Hotta",
year = "2007",
month = "3",
doi = "10.1210/jc.2006-1808",
language = "English",
volume = "92",
pages = "1145--1154",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - Functional single-nucleotide polymorphisms in the secretogranin III (SCG3) gene that form secretory granules with appetite-related neuropeptides are associated with obesity

AU - Tanabe, Atsushi

AU - Yanagiya, Takahiro

AU - Iida, Aritoshi

AU - Saito, Susumu

AU - Sekine, Akihiro

AU - Takahashi, Atsushi

AU - Nakamura, Takahiro

AU - Tsunoda, Tatsuhiko

AU - Kamohara, Seika

AU - Nakata, Yoshio

AU - Kotani, Kazuaki

AU - Komatsu, Ryoya

AU - Itoh, Naoto

AU - Mineo, Ikuo

AU - Wada, Jun

AU - Funahashi, Tohru

AU - Miyazaki, Shigeru

AU - Tokunaga, Katsuto

AU - Hamaguchi, Kazuyuki

AU - Shimada, Tatsuo

AU - Tanaka, Kiyoji

AU - Yamada, Kentaro

AU - Hanafusa, Toshiaki

AU - Oikawa, Shinichi

AU - Yoshimatsu, Hironobu

AU - Sakata, Toshiie

AU - Matsuzawa, Yuji

AU - Kamatani, Naoyuki

AU - Nakamura, Yusuke

AU - Hotta, Kikuko

PY - 2007/3

Y1 - 2007/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33947525459&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947525459&partnerID=8YFLogxK

U2 - 10.1210/jc.2006-1808

DO - 10.1210/jc.2006-1808

M3 - Article

C2 - 17200173

AN - SCOPUS:33947525459

VL - 92

SP - 1145

EP - 1154

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -