RESUMO
We report that a single-nucleotide polymorphism (SNP) in the gene (PTPN22) encoding the lymphoid protein tyrosine phosphatase (LYP), a suppressor of T-cell activation, is associated with type 1 diabetes mellitus (T1D). The variants encoded by the two alleles, 1858C and 1858T, differ in a crucial amino acid residue involved in association of LYP with the negative regulatory kinase Csk. Unlike the variant encoded by the more common allele 1858C, the variant associated with T1D does not bind Csk.
Assuntos
Diabetes Mellitus Tipo 1/genética , Proteínas Tirosina Fosfatases/metabolismo , Diabetes Mellitus Tipo 1/enzimologia , Marcadores Genéticos , Humanos , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Proteínas Tirosina Fosfatases/genéticaRESUMO
The acid phosphatase (ACP1) locus codes for a low molecular weight protein tyrosine phosphatase (LMPTP) that is found ubiquitously in human tissues. The *A allele of the ACP1 gene is associated with lower total enzymatic activity than the *B and *C alleles. An association between the *A allele and extreme values of body-mass-index (BMI) and dyslipidemia has previously been described in several samples of obese subjects from the Italian population. In the present study, we investigated the relationship between ACP1 *A allele genotypes (*A/*A, *A/*B, and *A/*C) and non-*A allele genotypes (*B/*B, *B/*C, and *C/*C) and metabolic variables in 277 Caucasian post-menopausal subjects consisting of 82 non-obese subjects (BMI/=35) subjects. ACP1 genotypes were found to be significantly associated with total cholesterol (p
Assuntos
Fosfatase Ácida/genética , Isoenzimas , Obesidade/enzimologia , Proteínas Tirosina Fosfatases/genética , Proteínas Proto-Oncogênicas , Triglicerídeos/metabolismo , Fosfatase Ácida/metabolismo , Análise de Variância , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/genética , Proteínas Tirosina Fosfatases/metabolismo , Triglicerídeos/sangueRESUMO
PURPOSE: The interaction between chemokines and their receptors is extremely important in controlling T cell migration into sites of CNS inflammation. Because trafficking of inflammatory T cells into the central nervous system (CNS) is a key player in the pathogenesis of multiple sclerosis (MS), we investigated the possible association of CCR5 delta32 deletion in this disorder. METHODS: DNA isolated from postmortem brain tissue samples of 132 patients with MS and from blood tissue samples of 163 gender and ethnicity-matched healthy controls was used to screen for the CCR5 delta32 deletion allele. RESULTS: An increased frequency of 32-bp deletion allele was found to be associated with early death (P = 0.00005) and with a progressive reduction in the years of survival (onset to death). The death hazard ratio of CCR5 with deletion versus no deletion was 2.12, suggesting that MS patients with the 32-bp deletion have twice the mortality rate of patients with the normal genotype. This effect was more significant in females (hazard ratio 3.58). CONCLUSION: A strong association of the CCR5delta32 deletion with early death could serve as a prognostic marker for MS.