CONICET | Buscador de Institutos y Recursos Humanos

Context: The kisspeptins are a family of peptides encoded by the KISS1 gene, which bind to the G-protein coupled receptor-54 (GPR54). KISS1 and its receptor have been shown to play a key role in controlling the onset of human puberty. Recently, we identify activating missense mutation in the coding regions of KISS1 and GPR54 in children with gonadotropin-dependent precocious puberty (GDPP). KISS1 promoter region includes an 1.1 kb conserved sequence upstream to the transcription start site that contains a number of potential consensus binding sites for different transcription factors, including TTF1 and SP1/SP3. Aim: To determine the role and frequency of potential nucleotide variants within KISS1 promoter region in a cohort of patients with idiopathic GDPP. Patients and Methods: Seventy five children (71 girls and 4 boys) with sporadic or familial idiopathic GDPP, in which GPR54 and KISS1 coding region had been previously screened, and 100 controls were studied. Genomic DNA was extracted and the promoter region of the KISS1 gene was amplified and automatically sequenced. The DNAs from control were studied by sequencing or digestion with restriction enzyme (MsI1). The comparison between the genotype and allele frequencies of the two selected groups was performed in contingency tables and chi-square test. Results: Five single nucleotide polymorphisms (SNPs) were detected in affected and control groups: -936delC, -463C>T, -424G>A, -362T>C, and -71G>A. The -936delC and -71G>A SNPs had not been previously described. Interestingly, the -71G>A SNP is located within a SP1 consensus binding sequence. However, genotype and allele frequencies of this SNP as well as the others were not statistically different between children with GDPP and controls. Conclusions: Two novel SNPs in the KISS1 promoter region (-936delC and -71G>A) were described. We conclude that KISS1 promoter SNPs were not associated with GDPP phenotype. This work has been supported by FAPESP.