Urinary beta-trace protein gene expression analysis in type 2 diabetes mellitus patients / Análise da expressão do gene da proteína beta-traço na urina de pacientes com diabetes mellitus tipo 2

ABSTRACT Objective: To evaluate the gene expression of beta-trace protein in urine of diabetic patients, with no reduction in glomerular filtration rate, which was defined as below 60mL/min/1.73m2. Methods: Type 2 diabetes mellitus patients were recruited, and a group of non-diabetic individuals served as control. Beta-trace protein gene expression was analyzed by quantitative PCR. Blood samples were collected to establish glucose levels and baseline kidney function. Accuracy was analyzed using ROC curves. Results: Ninety type 2 diabetes mellitus patients and 20 non-diabetic individuals were recruited. The area under the curve was 0.601, sensitivity of 20% and specificity of 89.47%. Among diabetic participants, 18% showed an expression above the cutoff point. Conclusion: These results of accuracy of beta-trace protein gene expression in urine of diabetic patients are promising, although they did not achieve a higher area under the curve level.

RESUMO Objetivo: Avaliar a expressão do gene da proteína beta-traço na urina de pacientes diabéticos, sem redução na taxa de filtração glomerular, definida como abaixo de 60mL/min/1,73m2. Métodos: Foram recrutados pacientes com diabetes mellitus tipo 2, e um grupo de indivíduos não diabéticos serviu como controle. A expressão do gene da proteína beta-traço foi analisada por PCR quantitativa. Amostras de sangue foram coletadas para estabelecer níveis de glicemia e função renal inicial. A acurácia foi analisada utilizando curvas ROC. Resultados: Foram recrutados 90 pacientes com diabetes mellitus tipo 2 e 20 não diabéticos. A área sob a curva foi de 0,601, com sensibilidade de 20% e especificidade de 89,47%. Entre os diabéticos, 18% apresentaram expressão acima do ponto de corte. Conclusão: Estes resultados de acurácia da expressão do gene da proteína beta-traço na urina de pacientes diabéticos são promissores, apesar de não terem atingido um nível alto na área sob a curva.

Common variants at the promoter region of the APOM confer a risk of rheumatoid arthritis

Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 x 10(-7)). Three more polymorphisms were identified at the promoter region of the APOM by the re-sequencing. For the replication, we genotyped the four SNP loci in the independent case-control set. The association of rs805297 identified by GWAS was successfully replicated (OR = 1.40, P = 6.65 x 10(-5)). The association became more significant in the combined analysis of discovery and replication sets (OR = 1.56, P = 2.73 +/- 10(-10)). The individuals with the rs805297 risk allele (A) at the promoter region showed a significantly lower level of APOM expression compared with those with the protective allele (C) homozygote. In the logistic regressions by the phenotype status, the homozygote risk genotype (A/A) consistently showed higher ORs than the heterozygote one (A/C) for the phenotype-positive RAs. These results indicate that APOM promoter polymorphisms are significantly associated with the susceptibility to RA.

Reproducción y fertilidad humana: aspectos biomédicos de la familia de las lipocalinas: biología, patobiología y bioclínica / Human reproduction and fertility: biomedical aspects of the lipocalin family: biology, pathobiology and bioclinic aspects

La familia de genes de las lipocalinas (LCN) está compuesta por varios miembros que comparten una estructura común y que se han duplicado en forma repetida durante la evolución expandiéndose a más de 150 genes conocidos, de ellos al menos veinte reportados en la especie humana. El grupo de proteínas de las LCN está constituido por varios elementos que comparten la propiedad común de unión de ligandos lipofílicos. Las LCN funcionan en un amplio rango de sistemas incluyendo quimiorrecepción y transporte en fisiología sensorial del gusto y olor, coloración, modulación hemato-inmune, síntesis de prostanglandina D2, neuro-fisiología, fisiología reproductiva y fertilidad, embriogénesis, proliferación y división celular, supervivencia y apoptosis celular. Es evidente su rol en patobiología y bioclínica reproductiva y de la fertilidad al observar que varias LCN tienen niveles alterados de expresión en diferentes eventos patofisiológicos. Esta revisión resume hallazgos e implicaciones

The family of the lipocalin (LCN) genes is composed by various members that share a common structure and haveduplicated repeatedly during evolution expanding to more than 150 known genes of which at least 20 have been reported in the human species. The group of lipocalin-related proteins is comprised by a number of elements which share various common properties such as binding to different lipophilic ligands. Lipocalins are involved in a broad range of systems including chemoreception and transport functions in sensory physiology of taste and smell, coloration, modulation of hemato-immune response, synthesis of prostaglandin D2, neurophysiology, physiology of reproduction and fertility, embryogenesis, cell proliferation and division, and cell survival and apoptosis. Its role is evident in the pathophysiology and bioclinical aspects of reproduction and fertility consistent with the observation of altered levels of expression of several lipocalins in different pathophysiological events. This review summarizes findings and implications on this topic.