Trans-Activation Response Element RNA is Detectable in the Plasma of a Subset of Aviremic HIV-1-Infected Patients.

Determining the HIV-1 reservoir size in infected individuals is of great importance for improvement of their treatment. Plasma trans-activation response element (TAR) RNA has been suggested as one of the possible biomarkers. TAR RNA is produced during non-processive transcription in HIV-1 productively infected and latent T cells. Here, plasma samples and paired exosome samples of 55 subjects from the observational SCOPE cohort were analysed for the presence of TAR RNA. First, a PCR-based assay was optimized, which provided 100% specificity and 100% sensitivity in differentiating HIV-1 infected non-controllers from uninfected individuals. Next, TAR RNA was detected in the plasma of 63% of aviremic HIV-1-infected patients, who were either treated with antiretroviral therapy or were elite controllers. Although TAR RNA levels did not correlate with patient gender, age, CD4 levels, CD8 levels, they tended to correlate with CD4/CD8 ratio (P = 0.047). This study is the first to investigate plasma TAR RNA in a relatively large cohort of HIV-1-infected patients. We additionally show that the TAR RNA molecules in the plasma of aviremic patients are not limited to exosomes.

Clinical Role of CYP2C19 Polymorphisms in Patients with Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency.

Extraadrenal enzymes such as CYP2C19 may participate in residual 21-hydroxylation of progesterone leading to milder phenotypes of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD). Among 94 21OHD patients 28 were homozygous or compound heterozygous for severe CYP21A2 mutations. We have reviewed their clinical phenotype and obtained information on maintenance doses of hydrocortisone and fludrocortisone. All patients were genotyped for CYP2C19*2 and CYP2C19*17 alleles. Eleven patients with CYP2C19*1/*17 genotype had all salt-wasting 21OHD. Among 17 patients with CYP2C19 genotypes leading to normal or decreased CYP2C19 activity, 15 had salt-wasting, one had simple virilizing and one had non-classical 21OHD. CYP2C19*1/*17 genotype was associated with lower maintenance dose of fludrocortisone (p = 0.04), but not of hydrocortisone (p > 0.05). Increased CYP2C19 activity could slightly ameliorate mineralocorticoid deficiency in 21OHD.

Gene-gene interactions in the folate metabolic pathway influence the risk for acute lymphoblastic leukemia in children.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Genetic polymorphisms in the folate metabolic pathway may contribute to the susceptibility to childhood ALL because they affect the DNA synthesis, methylation and repair. We analysed common genetic polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), methionine synthase (MS) and methionine synthase reductase (MTRR) in 68 children with ALL and 258 healthy controls to investigate their influence on the risk for ALL. No significant differences in frequencies of separate polymorphisms were observed between both groups. Combined MTHFR 677CT/TT and MS 2756AG/GG genotypes showed a nonsignificant tendency to reduce the risk for ALL 2.24-fold (CI: 0.191 - 1.037, P: 0.061). The risk was significantly reduced in carriers of combined MTHFR 677CT/TT, MS 2756AG/GG and MTRR 66AG/GG genotypes (OR: 0.312; CI: 0.107 - 0.907; P: 0.032). Our results suggest that gene - gene interactions that may decrease the methylation capacity might have a protective effect on the risk for childhood ALL.