RESUMO
BACKGROUND: The protein tyrosine phosphatase nonreceptor type 1 (PTPN1) gene encodes for the protein tyrosine phosphatase 1B, which suppresses the signaling pathway of insulin. Variations in PTPN1 may lead to changes in insulin sensitivity and consequent changes in protein tyrosine phosphatase 1B activity may also contribute to the development of metabolic endophenotypes. Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of the PTPN1 gene and metabolic endophenotypes and insulin sensitivity. DESIGN AND METHODS: We used data from a population-based cross-sectional study of 382 Dutch Caucasian men aged between 40-80 years, in whom we genotyped and analyzed four tag SNPs in PTPN1. RESULTS: We show that the minor alleles of three tag SNPs of the PTPN1 gene (rs6067484, rs6020611, rs1060402) are associated with higher levels of total plasma cholesterol and low-density lipoprotein (LDL) cholesterol in men with a body mass index (BMI) below 26 kg/m2 (P<0.05). We also show that men with a BMI below 26 kg/m2 and carrying the rs3487348 T allele tend to have a more beneficial profile for total plasma cholesterol and LDL cholesterol (P<0.05). Haplotypes that comprised these alleles were also borderline statistically significant associated with higher levels of LDL and total cholesterol in men with BMI below 26 kg/m2. CONCLUSION: Our results suggest that SNPs in the PTPN1 gene are associated with total plasma and LDL cholesterol levels.
Assuntos
LDL-Colesterol/sangue , Colesterol/sangue , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Pressão Sanguínea/genética , Índice de Massa Corporal , Estudos Transversais , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Resistência à Insulina/genética , Modelos Lineares , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/enzimologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Países Baixos , Fenótipo , Medição de Risco , Fatores de Risco , Circunferência da CinturaRESUMO
The protein tyrosine phosphatase nonreceptor type1 (PTPN1) gene encodes for the protein tyrosine phosphatase 1B, which suppresses the signaling pathway of leptin. Variations of the PTPN1 gene may lead to changes in leptin sensitivity and thereby influence eating behavior and measures of obesity. This study investigated the association between single-nucleotide polymorphisms (SNPs) of the PTPN1 gene and eating behavior and different measures of obesity, including visceral fat. We used data from a population-based, cross-sectional study of 382 Dutch white men aged 40-80 years. Self-reported macronutrient intake was collected with a food frequency questionnaire. Anthropometrical measurements included BMI, waist and hip circumference, total lean and fat mass measured with dual-energy X-ray absorptiometry, and visceral and subcutaneous fat measured with ultrasound. Associations were studied using linear regression analysis. There were no statistically significant associations of SNPs in the PTPN1 gene with dietary phenotypes or measures of obesity.
Assuntos
Adiposidade/genética , Ingestão de Energia/genética , Leptina/metabolismo , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Tecido Adiposo , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Dieta , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Países Baixos , Relação Cintura-QuadrilAssuntos
Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Resistência à Insulina , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Seleção de Pacientes , Aptidão Física , Valores de Referência , FumarRESUMO
Worldwide, the incidence of type 2 diabetes is rising rapidly, mainly because of the increase in the incidence of obesity, which is an important risk factor for this condition. Both obesity and type 2 diabetes are complex genetic traits but they also share some nongenetic risk factors. Hence, it is tempting to speculate that the susceptibility to type 2 diabetes and obesity might also partly be due to shared genes. By comparing all of the published genome scans for type 2 diabetes and obesity, five overlapping chromosomal regions for both diseases (encompassing 612 candidate genes) have been identified. By analysing these five susceptibility loci for type 2 diabetes and obesity, using six freely available bioinformatics tools for disease gene identification, 27 functional candidate genes have been pinpointed that are involved in eating behaviour, metabolism and inflammation. These genes might reveal a molecular link between the two disorders.
