J Korean Med Sci.  2017 Jan;32(1):108-114. 10.3346/jkms.2017.32.1.108.

Genetic Variations of the KISS1R Gene in Korean Girls with Central Precocious Puberty

• Oh YJ
• Rhie YJ
• Nam HK
• Kim HR
• Lee KH

• KMID: 2417592
• DOI: http://doi.org/10.3346/jkms.2017.32.1.108

Abstract

The timing of puberty onset varies greatly among individuals, and much of this variation is modulated by genetic factors. This study aimed to identify the kisspeptin receptor (KISS1R) gene variations and to investigate the associations between these variations and central precocious puberty (CPP). Korean girls with CPP (n = 194) and their healthy controls (n = 99) were included in this study. The entire coding region and the exon-intron boundaries (exon 1 through 5) of the KISS1R gene were directly sequenced. Seven polymorphisms were identified in the KISS1R gene. A missense change c.1091T>A, and an intron variant c.738+64G>T showed significantly higher allele frequencies in CPP patients than in controls (c.1091T>A: 30.7% vs. 22.2%, P = 0.031; c.738+64G>T: 45.6% vs. 35.9%, P = 0.023). The missense variant (c.1091T>A) was a nonsynonymous polymorphism that induces amino acid substitution of p.Leu364His. The haplotype CAGTGTC was detected more frequently in the CPP group (P = 0.042). The sequence variants of the KISS1R gene can be inducible factors in the development of CPP. The association between sequence variants and CPP should be validated by further evidence obtained from larger samples of children with CPP.

Keyword

KISS1R Gene; Precocious Puberty; Central; Polymorphism; Timing of Puberty

MeSH Terms

Adolescent
Amino Acid Substitution
Child
Clinical Coding
Female*
Gene Frequency
Genetic Variation*
Haplotypes
Humans
Introns
Puberty
Puberty, Precocious*

Figure

• 

  Fig. 1 LD plot for 7 SNPs in the KISS1R gene. The D′ values that correspond to each SNP pair are expressed as a percentage and shown within the respective square. Squares without numbers represent D′ values of 1.0, indicative of complete LD. The 7 SNPs constitute one haplotype block (Block 1). LD = linkage disequilibrium, KISS1R = kisspeptin receptor, D′ = linkage disequilibrium coefficient, SNP = single-nucleotide polymorphism.

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