RESUMO
The C825T single nucleotide polymorphism (SNP) in the guanine nucleotide-binding protein, beta polypeptide 3 ( GNB3) gene gives rise to a splice variant, GNB3s that has enhanced G protein activation and signal transduction activity. This variant has been reported to be associated with cardiovascular disease, diabetes and obesity. We studied this SNP in 95 healthy 18 to 30 year-old African American university students to determine its association with aerobic capacity and cardiorespiratory fitness as measured by peak oxygen consumption (VO (2)peak). We also tested the effect of heart rate variability (HRV) as an independent predictor of VO (2)peak. We tested the association of the SNP and HRV with VO (2)peak in a multivariate regression analysis with appropriate adjustments of covariates, under dominant and recessive models. We found a significant independent association of the 825T allele with VO (2)peak under the dominant model (beta-coef.=-0.101, P=0.0442). We also observed that HRV marginally influenced VO (2)peak. This finding suggests that GNB3 C825T polymorphism is associated with VO (2)peak which is influenced by autonomic modulation of heart rate in African Americans.
Assuntos
Proteínas Heterotriméricas de Ligação ao GTP/genética , Consumo de Oxigênio/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Negro ou Afro-Americano/genética , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Análise Multivariada , Análise de Regressão , Transdução de Sinais/genética , Estudantes , Universidades , Adulto JovemRESUMO
The aim of this study was to develop a saturated transcript map of the region encompassing the HPC1 locus to identify the susceptibility genes involved in hereditary prostate cancer (OMIM 176807) and hyperparathyroidism-jaw tumor syndrome (OMIM 145001). We previously reported the generation of a 6-Mb BAC/PAC contig of the candidate region and employed various strategies, such as database searching, exon-trapping, direct cDNA hybridization, and sample sequencing of BACs, to identify all potential transcripts. These efforts led to the identification and precise localization on the BAC contig of 59 transcripts representing 22 known genes and 37 potential transcripts represented by ESTs and exon traps. Here we report the detailed characterization of these ESTs into full-length transcript sequences, their expression pattern in various tissues, their genomic organization, and their homology to known genes. We have also identified an Alu insertion polymorphism in the intron of one of the transcripts. Overall, data on 13 novel transcripts and the human RGS8 gene (homologue of the rat RGS8 gene) are presented in this paper. Ten of the 13 novel transcripts are expressed in prostate tissue and represent positional candidates for HPC1.
Assuntos
Cromossomos Humanos Par 1 , Síndromes Neoplásicas Hereditárias/genética , Neoplasias da Próstata/genética , Proteínas RGS/genética , tRNA Metiltransferases/genética , Sequência de Aminoácidos , Animais , Mapeamento de Sequências Contíguas , DNA Complementar , Etiquetas de Sequências Expressas , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença , Genoma Humano , Humanos , Hiperparatireoidismo/genética , Neoplasias Maxilomandibulares/genética , Masculino , Dados de Sequência Molecular , Mutação , Neoplasias das Paratireoides/genética , Ratos , Homologia de Sequência de Aminoácidos , Transcrição GênicaRESUMO
Several hereditary disease loci have been genetically mapped to the chromosome 1q24-q31 interval, including the hereditary prostate cancer 1 (HPC1) locus. Here, we report the construction of a 20-Mb yeast artificial chromosome contig and a high-resolution 6-Mb sequence-ready bacterial artificial chromosome (BAC)/P1-derived artificial chromosome (PAC) contig of 1q25 by sequence and computational analysis, STS content mapping, and chromosome walking. One hundred thirty-six new STSs, including 10 novel simple sequence repeat polymorphisms that are being used for genetic refinement of multiple disease loci, have been generated from this contig and are shown to map to the 1q25 interval. The integrity of the 6-Mb BAC/PAC contig has been confirmed by restriction fingerprinting, and this contig is being used as a template for human chromosome 1 genome sequencing. A transcription mapping effort has resulted in the precise localization of 18 known genes and 31 ESTs by database searching, exon trapping, direct cDNA hybridization, and sample sequencing of BACs from the 1q25 contig. An additional 11 known genes and ESTs have been placed within the larger 1q24-q31 interval. These transcription units represent candidate genes for multiple hereditary diseases, including HPC1.