Association of ghrelin receptor gene polymorphism with bulimia nervosa in a Japanese population (original) (raw)

Summary.

Eating disorders (EDs) have a highly heterogeneous etiology and multiple genetic factors might contribute to their pathogenesis. Ghrelin, a novel growth hormone-releasing peptide, enhances appetite and increases food intake, and human ghrelin plasma levels are inversely correlated with body mass index. In the present study, we examined the 171T/C polymorphism of the ghrelin receptor (growth hormone secretagogue receptor, GHSR) gene in patients diagnosed with EDs, because the subjects having ghrelin gene polymorphism (Leu72Met) was not detected in a Japanese population, previously. In addition, β3 adrenergic receptor gene polymorphism (Try64Arg) and cholecystokinin (CCK)-A receptor (R) gene polymorphism (−81A/G, −128G/T), which are both associated with obesity, were investigated. The subjects consisted of 228 Japanese patients with EDs [96 anorexia nervosa (AN), 116 bulimia nervosa (BN) and 16 not otherwise specified (NOS)]. The age- and gender-matched control group consisted of 284 unrelated Japanese subjects. The frequency of the CC type of the GHSR gene was significantly higher in BN subjects than in control subjects (χ2 = 4.47, p = 0.035, odds ratio = 2.05, Bonferroni correction: p = 0.070), while the frequency in AN subjects was not different from that in controls. The distribution of neither β3 adrenergic receptor gene nor CCK-AR polymorphism differed between EDs and control subjects. Therefore, the CC type of GHSR gene polymorphism (171T/C) is a risk factor for BN, but not for AN.

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References

• InstitutionalAuthorNameAmerican Psychiatric Association (1994) Diagnostic and statistical manual of mental disordersEditionNumber4 American Psychiatric Press Washington, DC
  Google Scholar
• H Ariyasu K Takay T Tagami Y Ogawa K Hosoda T Akamizu M Suda T Koh K Natsui S Toyooka G Shirakami T Usui A Shimatsu K Doi H Hosoda M Kojima K Kangawa K Nakao (2001)ArticleTitleStomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans_J Clin Endocrinol Metab_ 86 4753–4758Occurrence Handle11600536Occurrence Handle1:CAS:528:DC%2BD3MXptVars70%3DOccurrence Handle10.1210/jc.86.10.4753
  Article PubMed CAS Google Scholar
• A Asakawa A Inui T Kaga H Yuzuriha T Nagata N Ueno S Makino M Fujimiya A Niijima A Fujino M Kasuga (2001)ArticleTitleGhrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin_Gastroenterology_ 120 337–345Occurrence Handle11159873Occurrence Handle1:CAS:528:DC%2BD3MXhtlKlt7Y%3DOccurrence Handle10.1053/gast.2001.22158
  Article PubMed CAS Google Scholar
• A Baessler MJ Hasinoff M Fischer W Reinghard GE Sonnenberg M Olivier J Erdmann H Schunkert A Doering HJ Jacob AG Commuzzie AH Kissebah AE Kwitek (2005)ArticleTitleGenetic linkage and association of the growth hormone secretagogue receptor (ghrelin receptor) gene in human obesity_Diabetes_ 54 259–267Occurrence Handle15616037Occurrence Handle1:CAS:528:DC%2BD2MXhtVWis7w%3D
  PubMed CAS Google Scholar
• A Funakoshi K Miyasaka H Matsumoto S Yamamori S Takiguchi K Kataoka Y Takata K Matsusue A Kono H Shimokata (2000)ArticleTitleGene structure of human cholecystokinin (CCK) type-A receptor: body fat content is related to CCK type-A receptor gene promoter polymorphism_FEBS Lett_ 466 264–266Occurrence Handle10682840Occurrence Handle1:CAS:528:DC%2BD3cXhtlCitbw%3DOccurrence Handle10.1016/S0014-5793(00)01080-2
  Article PubMed CAS Google Scholar
• DM Garner MP Olmsted Y Bohr PE Garfinkel (1982)ArticleTitleThe eating attitudes test: psychometric features and clinical correlates_Psychol Med_ 12 871–878Occurrence Handle6961471Occurrence Handle1:STN:280:DyaL3s7hvVWkug%3D%3DOccurrence Handle10.1017/S0033291700049163
  Article PubMed CAS Google Scholar
• A Hinney A Hoch F Geller H Schäfer W Siegfried H Goldschmidt H Remschmidt J Hebebrand (2002)ArticleTitleGhrelin gene: identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students_J Clin Endocrinol Metab_ 87 2716–2719Occurrence Handle12050239Occurrence Handle1:CAS:528:DC%2BD38XkvFaktLs%3DOccurrence Handle10.1210/jc.87.6.2716
  Article PubMed CAS Google Scholar
• M Koda F Ando N Niino H Shimokata K Miyasaka A Funakoshi (2004)ArticleTitleAssociation of cholecystokinin 1 receptor and β3-adrenergic receptor polymorphisms with midlife weight gain_Obesity Res_ 8 1212–1216
  Google Scholar
• H Koizumi K Hashimoto K Itoh M Nakazato E Himizu S Ohgake K Koike N Okamura S Matsushita K Suzuki M Murayama S Higuchi M Iyo (2004)ArticleTitleAssociation between the brain-derived neurotrophic factor 196GA polymorphism and eating disorders_Am J Med Genet_ 127B 125–127Occurrence Handle10.1002/ajmg.b.20153Occurrence Handle15108194
  Article PubMed Google Scholar
• M Kojima H Hosoda Y Date M Nakazato K Kangawa (1999)ArticleTitleGhrelin is a growth-hormone releasing acylated peptide from stomach_Nature_ 402 656–660Occurrence Handle10604470Occurrence Handle1:CAS:528:DC%2BD3cXjs1KiOccurrence Handle10.1038/45230
  Article PubMed CAS Google Scholar
• S Matsushita T Nakamura N Nishiguchi S Higuchi (2002)ArticleTitleAssociation of serotonin transporter regulatory region polymorphism and abnormal eating behaviors_Mol Psychiat_ 7 538–540Occurrence Handle1:CAS:528:DC%2BD38XlsFWrsbw%3DOccurrence Handle10.1038/sj.mp.4001028
  Article CAS Google Scholar
• S Matsushita K Suzuki M Murayama N Nishiguchi A Hishimoto A Takeda O Shirakawa S Higuchi (2004)ArticleTitleSerotonin transporter regulatory region polymorphism is associated with anorexia nervosa_Am J Med Genet_ 128B 114–117Occurrence Handle10.1002/ajmg.b.30022Occurrence Handle15211642
  Article PubMed Google Scholar
• K Miyasaka Y Yoshida S Matsushita S Higuchi K Maruyama N Niino F Ando H Shimokata S Ohta A Funakoshi (2004a)ArticleTitleAssociation of cholecystokinin-A receptor gene polymorphism with alcohol dependence in a Japanese population_Alco and Alco_ 39 25–28Occurrence Handle1:CAS:528:DC%2BD2cXns1Kq
  CAS Google Scholar
• K Miyasaka Y Yoshida S Matsushita S Higuchi O Shirakawa H Shimokata A Funakoshi (2004b)ArticleTitleAssociation of cholecystokinin-A receptor gene polymorphisms and panic disorder in Japanese_Am J Med Genet_ 127B 78–80Occurrence Handle10.1002/ajmg.b.20160
  Article Google Scholar
• M Nakazato N Murakami Y Date M Kojima H Matsuo K Kangawa S Matsukura (2001)ArticleTitleA role for ghrelin in the central regulation of feeding_Nature_ 409 194–198Occurrence Handle11196643Occurrence Handle1:CAS:528:DC%2BD3MXlvFSmsg%3D%3DOccurrence Handle10.1038/35051587
  Article PubMed CAS Google Scholar
• N Nishiguchi S Matsushita K Suzuki M Murayama O Shirakawa S Higuchi (2001)ArticleTitleAssociation between 5HT2A receptor gene promoter region polymorphism and eating disorders in Japanese patients_Biol Psychiatry_ 50 123–128Occurrence Handle11526993Occurrence Handle1:CAS:528:DC%2BD3MXlslCnsLw%3DOccurrence Handle10.1016/S0006-3223(00)01107-0
  Article PubMed CAS Google Scholar
• B Otto U Cuntz E Fruehauf R Wawarta C Folwaczny RL Riepl MI Heiman P Lehnert M Fiochter M Tschöp (2001)ArticleTitleWeight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa_Eur J Endocrin_ 145 R5–R9Occurrence Handle1:CAS:528:DC%2BD3MXosV2gs74%3D
  CAS Google Scholar
• H Shimokata Y Yamada M Nakagawa R Okubo T Saido A Funakoshi K Miyasaka S Ohta G Tsujimoto M Tanaka F Ando N Niino (2000)ArticleTitleDistribution of geriatric disease-related genotypes in the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA)J Epidem 10 IssueID[Suppl] 46–55
  Google Scholar
• M Tanaka T Naruo D Yasuhara Y Tatebe N Nagai T Shiiya M Nakazato S Matsukura S Nozoe (2003)ArticleTitleFasting plasma ghrelin levels in subtypes of anorexia nervosa_Psychoneuroendocrinol_ 28 829–835Occurrence Handle1:CAS:528:DC%2BD3sXlvVSgur4%3DOccurrence Handle10.1016/S0306-4530(02)00066-5
  Article CAS Google Scholar
• M Tshöp DL Smiley ML Heiman (2000)ArticleTitleGhrelin induces adiposity in rodents_Nature_ 407 908–913Occurrence Handle10.1038/35038090
  Article Google Scholar
• O Ukkola E Ravussin P Jacobson L Pérusse T Rankinen M Tschöp ML Heiman AS Leon DC Rao JS Skinner JH Wilmore L Sjöström C Bouchard (2002)ArticleTitleRole of ghrelin polymorphisms in obesity based on three different studies_Obes Res_ 10 781–791Occurrence Handle10.1038/oby.2002.106
  Article Google Scholar
• O Ukkola E Ravussin P Jacobson EE Snyder M Chagnon L Sjöström C Bouchard (2001)ArticleTitleMutations in the preproghrelin/ghrelin gene associated with obesity in humans_J Clin Endocrinol Metab_ 86 3996–3999Occurrence Handle11502844Occurrence Handle1:CAS:528:DC%2BD3MXlvFers7g%3DOccurrence Handle10.1210/jc.86.8.3996
  Article PubMed CAS Google Scholar
• T Umekawa T Yoshida N Sakane A Kogure M Kondo H Honjo (1999)ArticleTitleTrp64Arg mutation of β3-adrenoceptor gene deteriorates lipolysis induced by β3-adrenoceptor agonist in human omental adipocytes_Diabetes_ 48 117–120Occurrence Handle9892231Occurrence Handle1:CAS:528:DyaK1MXhvFSjsA%3D%3D
  PubMed CAS Google Scholar
• HJ Wang F Geller A Demplle N Achäuble S Friedel P Lichtner F Fontenla-Horro S Wudy S Hagemann L Gortner K Huse H Remschmidt T Bettechken T Meitinger H Schäfer J Hebebrand A Hinney (2004)ArticleTitleGhrelin receptor gene: identification of several sequence variants in extremely obese children and adolescents, healthy normal-weight and underweight students, and children with short normal stature_J Clin Endocrinol Metab_ 80 157–162Occurrence Handle10.1210/jc.2003-031395Occurrence Handle1:CAS:528:DC%2BD2cXmvFeqsw%3D%3D
  Article CAS Google Scholar
• AM Wren LJ Seal MA Cohen AE Brynes GS Frost KG Murphy WS Dhillo MA Ghatei SR Bloom (2001)ArticleTitleGhrelin enhances appetite and increases food intake in humans_J Clin Endocrinol Metab_ 86 5992–5995Occurrence Handle11739476Occurrence Handle1:CAS:528:DC%2BD3MXptVyksLg%3DOccurrence Handle10.1210/jc.86.12.5992
  Article PubMed CAS Google Scholar
• AM Wren CJ Small HL Ward KG Murphy CL Dakin S Taheri AR Kennedy GH Robers DG Morgan MA Ghatai SR Bloom (2000)ArticleTitleThe novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion_Endocrinology_ 141 4325–4328Occurrence Handle11089570Occurrence Handle1:CAS:528:DC%2BD3cXnslKgsLw%3DOccurrence Handle10.1210/en.141.11.4325
  Article PubMed CAS Google Scholar
• T Yoshida N Sakane T Umekawa M Sakai T Takahashi M Kondo (1995)ArticleTitleMutation of β3-adrenergic-receptor gene and response to treatment of obesity_The Lancet_ 346 1433–1434Occurrence Handle1:STN:280:DyaK28%2FnsFCktQ%3D%3DOccurrence Handle10.1016/S0140-6736(95)92452-3
  Article CAS Google Scholar

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Authors and Affiliations

1. Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
   K. Miyasaka, H. Hosoya, A. Sekime & M. Ohta
2. Department of Social Participation and Health Promotion, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
   H. Amono
3. National Hospital Organization, Kurihama Alcoholism Center, Yokosuka, Japan
   S. Matsushita, K. Suzuki & S. Higuchi
4. Department of Gastroenterology, Kyushu Cancer Center, Fukuoka, Japan
   A. Funakoshi

Authors

1. K. Miyasaka
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2. H. Hosoya
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3. A. Sekime
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4. M. Ohta
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5. H. Amono
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6. S. Matsushita
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7. K. Suzuki
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8. S. Higuchi
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9. A. Funakoshi
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Miyasaka, K., Hosoya, H., Sekime, A. et al. Association of ghrelin receptor gene polymorphism with bulimia nervosa in a Japanese population.J Neural Transm 113, 1279–1285 (2006). https://doi.org/10.1007/s00702-005-0393-2

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• Received: 20 July 2005
• Accepted: 09 October 2005
• Published: 16 December 2005
• Issue Date: September 2006
• DOI: https://doi.org/10.1007/s00702-005-0393-2