Aims: The GPR54 gene has been proved to be important in the process of puberty onset, yet no association study has been performed to evaluate the effect of polymorphisms in the gene on central precocious puberty (CPP). This study was designed to scan for polymorphisms in the GPR54 gene and to investigate the relationships between the genotypes of GPR54 and the disease. Methods: 272 Chinese Han girls diagnosed to be CPP patients were recruited as the case group and 288 unrelated normal Chinese Han girls as the control group. The whole GPR54 gene was directly sequenced in randomly selected case samples, and the polymorphisms identified were genotyped by ligase detection reaction in both groups. Distributions of the polymorphisms and haplotypes were calculated for statistical evaluation. Results: Totally 6 polymorphisms were found in sequencing, one of which is a nonsynonymous mutation, while genotyping declared that another SNP located in the promoter region was statistically related to the disease (p = 0.037). Conclusion: One polymorphism in GPR54 gene might be correlated with some cases of CPP, likely by changes in expression of the receptor, but the moderate p value and the lack of functional data make it hard to confirm the correlation. Further studies on the polymorphisms are needed for the exact mechanism.

Cai DP: Precocious and Delayed Puberty in Children, ed 1. Fudan, Fudan University Press, 2003, p 35.
Petridou E, Syrigou E, Toupadaki N, Zavitsanos X, Willett W, Trichopoulos D: Determinants of age at menarche as early life predictors of breast cancer risk. Int J Cancer 1996;68:193–198.
Yu WH, Kimura M, Walczewaka A: Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci USA 1997;94:1023–1028.
Kadlubar FF, Berkowitz SG, Delongchamp RR, Charles W, Green LB, George T, Jatinder L, Erin S, Mary SW: The CYP3A4*1B variant is related to the onset of puberty, a known risk factor for the development of breast cancer. Cancer Epidemiol Biomarkers Prev 2003;12:327–331.
Xin X, Luan X, Xiao J, Wei D, Wang J, Lu D, Yang S: Association study of four activity SNPs of CYP3A4 with the precocious puberty in Chinese girls. Neurosci Lett 2005;381:284–288.
Barker-Gibb M, Plant TM, White C, Lee PA, Witchel SF: Genotype analysis of the neuropeptide Y (NPY) Y1 and NPY Y5 receptor genes in gonadotropin-releasing hormone-dependent precocious gonadarche. Fertil Steril 2004;82:491–494.
Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden J-M, Le Poul E, Brezillon S, Tyldesley R, Suarez-Huerta N, Vandeput F, Blanpain C, Schiffmann SN, Vassart G, Parmentier M: The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 2001;276:34631–34636.
Navarro VM, Casteliano JM, Fernandez-Fernandez R, Barreiro ML, Roa J, Sanchez-Criado JE, Aguilar E, Dieguez C, Pinilla L, Tena-Sempere M: Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide. Endocrinology 2004;145:4565–4574.
Shahab M, Mastronardi C, Seminara SB, Crowley WF, Ojeda SR, Plant TM: Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates. Proc Natl Acad Sci USA 2005;102:2129–2134.
Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J, Thresher RR, Malinge I, Lomet D, Carlton MBL, Colledge WH, Caraty A, Aparicio SAJR: Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci USA 2005;102:1761–1766.
Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, Zahn D, Dixon J, Kaiser UB, Slaugenhaupt SA, Gusella JF, O’Rahilly S, Carlton MBL, Crowley WF Jr, Aparicio SAJR, Col- ledge WH: The GPR54 gene as a regulator of puberty. New Engl J Med 2003;349:1614–1627.
de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E: Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA 2003;100:10972–10976.
Semple RK, Achermann JC, Ellery J, Farooqi IS, Karet FE, Stanhope RG, O’Rahilly S, Aparicio SA: Two novel missense mutations in G protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadism. J Clin Endocr Metab 2004;90:1849–1855.
Zhang LJ: Diagnosis and treatment of precocious puberty. J Pract Training Med 2005;33:5–6.
Oerter KE, Uriarte MM, Rose SR, Barnes KM, Cutler GB Jr: Gonadotropin secretory dynamics during puberty in normal girls and boys. J Clin Endocr Metab 1990;71:1251–1258.
Xiao Z, Xiao J, Jiang Y, Zhang S, Yu M, Zhao J, Wei D, Cao H: A novel method based on ligase detection reaction for low abundant YIDD mutants detection in hepatitis B virus. Hepatol Res 2006;34:150–155.
Stephens M, Smith NJ, Donnelly P: A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001;68:978–989.
Belchetz PE, Plant TM, Nakai Y, Keogh EJ, Knobil E: Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone. Science 1978;202:631–633.
Davis KL, Charney D, Coyle JT, Nemeroff C: Neuropsychopharmacology: The Fifth Generation of Progress, ed 5. Philadelphia, Lippincott Williams & Wilkins, 2002, chap 17, pp 218–228.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.