Search

Aims: Circulating vitamin D is linked with the risk of cardiovascular disease (CVD). A meta-analysis has yet to explicitly explore correlation between vitamin D and the risk of CVD incidence and recurrent CVD. This meta-analysis examines the association between 25-hydroxy-vitamin D (25(OH)D) and the risk of CVD incidence (fatal, non-fatal, fatal and non-fatal combined events) and the risk of recurrent CVD (fatal, recurrent, and fatal and recurrent combined events). PROSPERO registration-CRD42021251483., Data Synthesis: A total of 79 studies (46 713 CVD cases in 1 397 831 participants) were included in the meta-analysis, of which 61 studies examined the risk of CVD incidence events, and 18 studies examined risk of recurrent CVD events. The risk of CVD incidence events (RR = 1.34, 95% CI: 1.26-1.43, p < 0.001) and recurrent CVD events (RR = 1.86, 95% CI: 1.46-2.36, p < 0.001) was higher in the lowest than the highest category of circulating 25(OH)D. Dose-response analysis reported a linear association for every 10 ng/ml increment of 25(OH)D and non-fatal CVD incidence events (RR = 0.94; 95% CI = 0.89-0.98, p = 0.005), lower fatal recurrent CVD events (RR = 0.45; 95% CI = 0.32-0.62, p < 0.001) and lower combined recurrent CVD events (RR = 0.80; 95% CI = 0.65-0.97, p = 0.023). A non-linear association was observed between higher 25(OH)D and lower fatal CVD incidence events (P-nonlinear<0.001), lower combined CVD incidence events (P-nonlinear = 0.001), and lower non-fatal recurrent CVD events (P-nonlinear = 0.044)., Conclusions: The lowest category of circulating 25(OH)D was associated with a higher risk of CVD incidence events and recurrent CVD events., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Adenylate kinase (AK) deficiency is a rare erythroenzymopathy associated with hereditary nonspherocytic haemolytic anaemia along with mental/psychomotor retardation in few cases. Diagnosis of AK deficiency depends on the decreased level of enzyme activity in red cell and identification of a mutation in the AK1 gene. Until, only eight mutations causing AK deficiency have been reported in the literature. We are reporting two novel missense mutation (c.71A > G and c.413G > A) detected in the AK1 gene by next-generation sequencing (NGS) in a 6-year-old male child from India. Red cell AK enzyme activity was found to be 30% normal. We have screened a total of 32 family members of the patient and showed reduced red cell enzyme activity and confirm mutations by Sanger's sequencing. On the basis of Sanger sequencing, we suggest that the proband has inherited a mutation in AK1 gene exon 4 c.71A > G (p.Gln24Arg) from paternal family and exon 6 c.413G > A (p.Arg138His) from maternal family. Bioinformatics tools, such as SIFT, Polymorphism Phenotyping v.2, Mutation Taster, MutPred, also confirmed the deleterious effect of both the mutations. Molecular modelling suggests that the structural changes induced by p.Gln24Arg and p.Arg138His are pathogenic variants having a direct impact on the structural arrangement of the region close to the active site of the enzyme. In conclusion, NGS will be the best solution for diagnosis of very rare disorders leading to better management of the disease. This is the first report of the red cell AK deficiency from the Indian population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)