Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies.

Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10-8) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52-0.73; P-value = 9.62 × 10-9). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55-0.76, P-value = 3.25 × 10-8). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.

Role of Vitamin D in Hospitalized Children With Lower Tract Acute Respiratory Infections.

BACKGROUND: Vitamin D is known to have modulatory actions in the immune system. Its influence on the severity of lower tract acute respiratory infections (LT-ARIs) is unclear. OBJECTIVES: The aim of the present study was to evaluate the role of vitamin D on LT-ARI in paediatric patients. METHODS: Children admitted to hospital with LT-ARI were prospectively recruited through the GENDRES network (March 2009-May 2013). The 25-hydroxyvitamin D (25-OHD) levels were measured by immunoassay. The severity of the illness was evaluated according to clinical scales, length of hospital stay, ventilatory requirements, and pediatric intensive care unit admission. RESULTS: A total of 347 patients with a median (interquartile range) age of 8.4 (2.6-21.1) months were included. The mean (SD) 25-OHD levels in our series were 27.1 (11.3) ng/mL. In this study, a cutoff value of ≥30 ng/mL was considered optimal vitamin status. Patients with 25-OHD levels <20 ng/mL were at a higher risk of showing severe signs of respiratory difficulties (OR 5.065, 95% confidence interval 1.998-12.842; P = 0.001) than patients with normal values, and had a 117% higher risk of oxygen necessity and 217% higher risk of ventilatory requirement than those patients with normal values. An inverse correlation was found between 25-OHD levels and the severity in the evaluated scales. 25-OHD levels did not influence PICU admission rate or length of hospital stay. CONCLUSIONS: 25-OHD levels of children admitted because of a LT-ARI are <30 ng/mL. Lower levels of 25-OHD were found to be correlated with severity of the disease. The possible role of abnormal 25-OHD levels as a facilitator or consequence of the infection needs further evaluation.