Regional solar radiation is inversely correlated with incidence and severity of tuberculosis in Chile.

Vitamin D (VD) deficiency has been linked to increased incidence and morbidity of tuberculosis (TB). Chile has large variations in solar radiation (SR; a proxy of VD status) and high prevalence of VD deficiency in its southernmost regions with low SR. We investigated the correlation between regional SR and rates of TB incidence, admissions and deaths in Chile by reviewing national records on prospectively collected mandatory disease notifications, admissions and mortality between 2001 and 2011. Over the study period, 26 691 new TB notifications were registered. The TB incidence rate was 14·77 (95% confidence intervals (CIs) 14·60-14·95), admission rate was 12·12 (95% CI 11·96-12·28) and mortality rate was 1·61 (95% CI 1·55-1·67) per 100 000 population per year. Multivariable linear regressions adjusting for significant demographic TB risk factors in Chile (regional prevalence of HIV infection, rates of migration from TB-endemic countries and rates of imprisonment) revealed an independent and highly statistically significant inverse association between SR and TB incidence rate (ß -1·05, 95% CI -1·73 to -0·36, P = 0·007), admission rate (ß -1·58, 95% CI -2·23 to -0·93, P < 0·001), and mortality rate (ß -0·15, 95% CI -0·23 to -0·07, P = 0·002). These findings support a potential pathogenic role of VD deficiency in TB incidence and severity.

Association between Gc genotype and susceptibility to TB is dependent on vitamin D status.

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)-gamma 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; p = 0.009). This association was preserved if serum 25(OH)D was <20 nmol.L(-1) (p = 0.01) but not if serum 25(OH)D was > or =20 nmol.L(-1) (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.