Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB).The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-c release assays were also performed on 36 Gujarati Asian TB contacts.The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p50.009). This association was preserved if serum 25(OH)D was ,20 nmol?L -1 (p50.01) but not if serum 25(OH)D was o20 nmol?L -1 (p50.36).Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-c release in Gujarati Asian TB contacts (p50.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied. Vitamin D metabolites in the circulation are bound to vitamin D binding protein (DBP), a highly expressed multifunctional 58-kDa serum glycoprotein encoded on chromosome 4. The DBP locus is among the most polymorphic known [6]. Two common polymorphisms at codons 416 (GATRGAG, AspRGlu) and 420 (ACGRAAG, ThrRLys) of exon 11 of the DBP gene (defined by the presence of restriction endonuclease sites for HaeIII and StyI, respectively) give rise to the three major electrophoretic variants of DBP, termed group-specific component 1 fast (Gc1F), Gc1 slow (Gc1S) and Gc2. These variants differ in their functional characteristics: the Gc1F and Gc1S variants have been reported to have greater affinity for 25(OH)D than the Gc2 variant [7], potentially leading to more efficient delivery of 25(OH)D to the target tissues, while the Gc2 variant is associated with decreased circulating concentrations of 25(OH)D, 1,25(OH) 2 D and DBP [8,9]. We therefore reasoned that possession of the Gc2 variant of DBP might associate with susceptibility to TB, and conducted

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Tuberculosis (TB) is one of the most common infectious diseases in the world. Mycobacterium tuberculosis infection leads to pulmonary active disease in approximately 5–10% of exposed individuals. Both bacteria- and host-related characteristics influence latent infection and disease. Host genetic predisposition to develop TB may involve multiple genes and their polymorphisms. It was reported previously that interferon gamma (IFN-γ) and nitric oxide synthase 2 (NOS2) are expressed on alveolar macrophages from TB patients and are responsible for bacilli control; thus, we aimed this study at genotyping single nucleotide polymorphisms IFNG+874T/A SNP and NOS2A-954G/C SNP to estimate their role on TB susceptibility and determine whether these polymorphisms influence serum nitrite and NOx − production. This case-control study enrolled 172 TB patients and 179 healthy controls. Neither polymorphism was associated with susceptibility to TB. NOS2A-954G/C SNP was not associated with serum levels of nitrite and NOx −. These results indicate that variants of IFNG+874T/A SNP and NOS2A-954G/C SNP do not influence TB susceptibility or the secretion of nitric oxide radicals in the study population.

The aim of the present study was to investigate the role of central 5-HT3 receptors on the control of blood glucose in stressed and non-stressed rats in both fasted and fed states. Adult Wistar male rats had each their third ventricle cannulated 7 days before the experiments. Injections of m-CPBG, a selective 5-HT3 receptor agonist, induced a significant increase in blood glucose in non-stressed rats in both fasted and in fed states. The same procedure was unable to modify stress-induced hyperglycemia. The hyperglycemic effect of m-CPBG central administration was blocked by pretreatment with ondansetron, a specific 5-HT3 receptor antagonist, indicating that the effects here obtained with m-CPBG were a result of its interaction with 5-HT3 receptors. Third ventricle injections of ondansetron alone were not able to modify blood glucose in non-stressed animals and did not change the hyperglycemic responses observed after immobilization stress. We conclude that pharmacological activation of the central 5-HT3 receptor induces a hyperglycemic effect in non-stressed animals.

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