Meta-Analysis of the Association Between the rs228570 Vitamin D Receptor Gene Polymorphism and Arterial Hypertension Risk.

The association between FokI polymorphism in the vitamin D receptor (VDR) gene and susceptibility to arterial hypertension (HT) is controversial. Thus, we evaluated the relation between FokI and HT according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using MEDLINE® (Medical Literature Analysis and Retrieval System Online)/PubMed, Scopus, and Cochrane Library CENTRAL databases. Data from case-control studies, including the number of participants, age, 25-hydroxyvitamin D concentrations, systolic and diastolic blood pressure values, FokI allele, and genotype frequency were extracted by 2 independent authors and OR was calculated with the 95% CI to assess the strength of the association between the FokI variant and odds of HT. In general and subgroup analyses, we used allelic (f compared with F), common (ff compared with FF + Ff), risk (ff + Ff compared with FF), and additive (ff compared with FF) models. Six case-control studies including 3140 cases and 3882 controls were reviewed in the meta-analysis. Global assessment revealed a correlation between FokI and reduced odds of HT in the additive/homozygote model (ff compared with FF; OR: 0.65; 95% CI: 0.45-0.94) and common/recessive model (ff compared with FF + Ff; OR: 0.75; 95% CI: 0.57-0.99). In Asian subjects, there was a significant reduction in the odds of HT in additive (ff compared with FF; OR: 0.84; 95% CI: 0.73-0.98) and risk models (ff + Ff compared with FF; OR: 0.87, 95% CI: 0.78-0.97), in particular, for Indians (South). In Africans, the statistically significant association occurred in the additive and common models. Allele f in the FokI polymorphism of the VDR gene was associated with reduced odds of HT in the general population based on the risk model. Thus, nutritional genomics can help understand the influence of nutrition on metabolic homeostasis pathways and the clinical consequences of hypertension. This study shows the need for healthy, anti-inflammatory, and antioxidant compounds to prevent or treat chronic complications.

Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs.

There is little evidence that current control strategies for canine leishmaniosis (CanL), the veterinary disease caused by L. infantum infection, are having a positive impact. This is of critical importance because dogs are a primary reservoir for L. infantum and a significant source of parasite transmission to humans. Drugs intended primarily for human use are prohibited for the treatment of CanL because of concerns over the propagation of resistant parasites. Although allopurinol effectively decreases parasite burden in CanL the treatment needs to be maintained for life. We hypothesized that during the allopurinol-induced parasite reduction dogs may become capable of developing a more robust immune response that may permit more effective control of parasites. To test this, we investigated the clinical and parasitological impact of short-term treatment with allopurinol, either alone or in combination with a defined subunit vaccine, on dogs naturally infected with L. infantum. A total of 28 dogs were distributed as follows: untreated; oral allopurinol alone (20 mg/kg, once each day for 90 days); or allopurinol with immunization with the Leish-F2 antigen formulated with the Toll-like receptor (TLR) 4 agonist Second generation Lipid Adjuvant (SLA) in stable emulsion (SE; SLA-SE). Dogs that did not receive treatment had a progressive decline in their clinical condition and an increase in their infection levels, while treatment with allopurinol alone alleviated the clinical symptoms of CanL but did not generate sustained reduction in parasites. Concomitant immunization with Leish-F2 + SLA-SE, however, improved clinical condition while also providing long-term clearance of L. infantum from lymphoid tissues and systemic organs. These results have important implications for both the management of CanL and for limiting L. infantum transmission to humans.