Fibromodulin Gene Variants (FMOD) as Potential Biomarkers for Prostate Cancer and Benign Prostatic Hyperplasia.

By the year 2050, the world's elderly population may increase exponentially, raising the rate of disease characteristic of this group, such as prostate cancer (PCa) and benign prostatic hyperplasia (BPH). Prostate disorders have a multifactorial etiology, especially age and genetic factors. Currently, PCa is the second most frequent neoplasm in the male population worldwide. The fibromodulin gene encodes a small leucine-rich proteoglycan (SLRP) which acts in the collagen fibrillogenesis pathway, cell adhesion, and modulation of TGF-ß signaling pathways, which has been recently associated with PCa. The present study sequenced the coding region of the FMOD in a sample of 44 PCa, 90 BPH, and 82 controls from a Brazilian population, and the results identified 6 variants: 2 missenses (p.(Tyr42Ser) and p.(Pro24Ala)); 3 synonymous (p.(His253=), p.(Asn353=), and p.(Glu79=)); and 1 intronic (c.980-114A>G). Of these, p.(Tyr42Ser), p.(Pro24Ala), and p.(Asn353=) are rare variants, and p.(Tyr42Ser) was predicted as potential pathogenic by the algorithms used here, in addition to not being observed in controls, suggesting that may be a potential biomarker for development of PCa and BPH. In conclusion, we identified for the first time, in Brazilian individuals with PCa and BPH, a potentially pathogenic variant in the analysis of FMOD gene. Further studies are needed to investigate the deleterious effect of this variant on the structure and/or function of the FMOD protein.

Dynamics of nonstructural glycoprotein-1 in dengue patients presenting with different clinical manifestations from 1986 to 2012 in Rio de Janeiro, Brazil.

The hyperendemicity and co-circulation of different dengue serotypes in Brazil have increased the number of severe dengue cases and the rate of hospitalization for dengue. Virological and individual factors are associated with the complexity of the disease. Antigenemia levels of nonstructural glycoprotein-1 (NS1) have been associated with severe dengue. Aiming to identify a severity marker during the acute phase (days 0 to 5 of disease), the association of NS1 antigenemia with clinical presentation, sex, age range, immune response, number of days of disease, and serotype RNA levels was evaluated in serum samples of patients from the state of Rio de Janeiro clinically classified as having dengue without warning signs (DWWS) or dengue with warning signs/severe dengue (DWWS/SD). The immune response was classified by in-house enzyme-linked immunosorbent assay, antigenemia was determined by quantification of NS1, and viremia was quantified by real-time PCR. Of the total number of patients, 36.6% (74 of 202) presented warning signs/severe dengue and 72.3% (146 of 202) were classified with primary infection. DENV-2 presented an association between clinical presentation and antigenemia (P = 0.02). DENV-3 had higher levels of NS1 (P < 0.0001). This study has shown that the infecting serotype influences circulating NS1 levels in the host, as well as NS1 antigenemia may vary as to the clinical presentation of the patient infected with DENV-2. However, the criterion used to screen patients for clinical presentation, in DWWS and DWWS/SD patients, was not a good marker for dengue severity in our study.