J Korean Med Sci.  2014 Aug;29(8):1120-1125. 10.3346/jkms.2014.29.8.1120.

KISS1 Gene Polymorphisms in Korean Girls with Central Precocious Puberty

• Rhie YJ
• Lee KH
• Ko JM
• Lee WJ
• Kim JH
• Kim HS

• KMID: 2129608
• DOI: http://doi.org/10.3346/jkms.2014.29.8.1120

Abstract

Kisspeptin/G-protein couple receptor-54 (GPR54) system plays a key role in the activation of the gonadotropic axis at puberty. Central precocious puberty (CPP) is caused by the premature activation of hypothalamic gonadotropin-releasing hormone secretion. This study was aimed to identify KISS1 gene variations and to investigate the associations between KISS1 gene variations and CPP in Korean girls. All coding exons of KISS1 gene were sequenced in Korean girls with CPP (n = 143) and their healthy controls (n = 101). Nine polymorphisms were identified in KISS1 gene. A novel single-nucleotide polymorphism (SNP), 55648176 T/G, was identified for the first time. SNP 55648184 C/G and 55648186 -/T were detected more frequently in CPP group than in control group. SNP 55648176 T/G was detected less frequently in CPP group than in control group. Haplotype GGGC-ACCC was detected less frequently in CPP group. The genetic variations of KISS1 gene can be contributing factors of development of CPP. The association between the gene variations and CPP should be validated by further evidence obtained from large-scaled and functional studies.

Keyword

KISS1 Gene; Kisspeptins; G-Protein Coupled Receptor-54; Precocious Puberty, Central

MeSH Terms

Base Sequence
Child
Female
Genetic Markers/genetics
Genetic Predisposition to Disease/*epidemiology/*genetics
Humans
Kisspeptins/*genetics
Molecular Sequence Data
Point Mutation/genetics
Polymorphism, Single Nucleotide/*genetics
Prevalence
Puberty, Precocious/*epidemiology/*genetics
Reproducibility of Results
Republic of Korea/epidemiology
Risk Assessment
Sensitivity and Specificity
Genetic Markers
Kisspeptins

Reference

1. Delemarre-van de Waal HA. Secular trend of timing of puberty. Endocr Dev. 2005; 8:1–14.

2. Terasawa E, Fernandez DL. Neurobiological mechanisms of the onset of puberty in primates. Endocr Rev. 2001; 22:111–151.

3. Ojeda SR, Lomniczi A, Mastronardi C, Heger S, Roth C, Parent AS, Matagne V, Mungenast AE. Minireview: the neuroendocrine regulation of puberty: is the time ripe for a systems biology approach? Endocrinology. 2006; 147:1166–1174.

4. 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 U S A. 2003; 100:10972–10976.

5. Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, Brézillon S, Tyldesley R, Suarez-Huerta N, Vandeput F, et al. 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.

6. Lee JH, Miele ME, Hicks DJ, Phillips KK, Trent JM, Weissman BE, Welch DR. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst. 1996; 88:1731–1737.

7. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003; 349:1614–1627.

8. 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 Endocrinol Metab. 2005; 90:1849–1855.

9. 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 U S A. 2005; 102:2129–2134.

10. Navarro VM, Castellano JM, García-Galiano D, Tena-Sempere M. Neuroendocrine factors in the initiation of puberty: the emergent role of kisspeptin. Rev Endocr Metab Disord. 2007; 8:11–20.

11. Rhie YJ, Lee KH, Eun SH, Choi BM, Chae HW, Kwon AR, Lee WJ, Kim JH, Kim HS. Serum kisspeptin levels in Korean girls with central precocious puberty. J Korean Med Sci. 2011; 26:927–931.

12. De Vries L, Shtaif B, Phillip M, Gat-Yablonski G. Kisspeptin serum levels in girls with central precocious puberty. Clin Endocrinol (Oxf). 2009; 71:524–528.

13. Papathanasiou A, Hadjiathanasiou C. Precocious puberty. Pediatr Endocrinol Rev. 2006; 3:182–187.

14. Kauli R, Galatzer A, Kornreich L, Lazar L, Pertzelan A, Laron Z. Final height of girls with central precocious puberty, untreated versus treated with cyproterone acetate or GnRH analogue: a comparative study with re-evaluation of predictions by the Bayley-Pinneau method. Horm Res. 1997; 47:54–61.

15. De Vries L, Kauschansky A, Shohat M, Phillip M. Familial central precocious puberty suggests autosomal dominant inheritance. J Clin Endocrinol Metab. 2004; 89:1794–1800.

16. Palmert MR, Boepple PA. Variation in the timing of puberty: clinical spectrum and genetic investigation. J Clin Endocrinol Metab. 2001; 86:2364–2368.

17. Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, Xu S, Seminara SB, Mendonca BB, Kaiser UB, Latronico AC. A GPR54-activating mutation in a patient with central precocious puberty. N Engl J Med. 2008; 358:709–715.

18. Ko JM, Lee HS, Hwang JS. KISS1 gene analysis in Korean girls with central precocious puberty: a polymorphism, p.P110T, suggested to exert a protective effect. Endocr J. 2010; 57:701–709.

19. Luan X, Zhou Y, Wang W, Yu H, Li P, Gan X, Wei D, Xiao J. Association study of the polymorphisms in the KISS1 gene with central precocious puberty in Chinese girls. Eur J Endocrinol. 2007; 157:113–118.

20. Silveira LG, Noel SD, Silveira-Neto AP, Abreu AP, Brito VN, Santos MG, Bianco SD, Kuohung W, Xu S, Gryngarten M, et al. Mutations of the KISS1 gene in disorders of puberty. J Clin Endocrinol Metab. 2010; 95:2276–2280.

21. West A, Vojta PJ, Welch DR, Weissman BE. Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene (KISS1). Genomics. 1998; 54:145–148.

22. Lanfranco F, Gromoll J, von Eckardstein S, Herding EM, Nieschlag E, Simoni M. Role of sequence variations of the GnRH receptor and G protein-coupled receptor 54 gene in male idiopathic hypogonadotropic hypogonadism. Eur J Endocrinol. 2005; 153:845–852.

23. Tenenbaum-Rakover Y, Commenges-Ducos M, Iovane A, Aumas C, Admoni O, de Roux N. Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54. J Clin Endocrinol Metab. 2007; 92:1137–1144.