ABSTRACT
OBJECTIVE: To undertake a genome-wide association study (GWAS) to identify genetic variants for stroke in an Indian population. METHODS: In a hospital-based case-control study, 8 teaching hospitals in India recruited 4,088 participants, including 1,609 stroke cases. Imputed genetic variants were tested for association with stroke subtypes using both single-marker and gene-based tests. Association with vascular risk factors was performed with logistic regression. Various databases were searched for replication, functional annotation, and association with related traits. Status of candidate genes previously reported in the Indian population was also checked. RESULTS: Associations of vascular risk factors with stroke were similar to previous reports and show modifiable risk factors such as hypertension, smoking, and alcohol consumption as having the highest effect. Single-marker-based association revealed 2 loci for cardioembolic stroke (1p21 and 16q24), 2 for small vessel disease stroke (3p26 and 16p13), and 4 for hemorrhagic stroke (3q24, 5q33, 6q13, and 19q13) at p < 5 × 10-8. The index single nucleotide polymorphism of 1p21 is an expression quantitative trait locus (p lowest = 1.74 × 10-58) for RWDD3 involved in SUMOylation and is associated with platelet distribution width (1.15 × 10-9) and 18-carbon fatty acid metabolism (p = 7.36 × 10-12). In gene-based analysis, we identified 3 genes (SLC17A2, FAM73A, and OR52L1) at p < 2.7 × 10-6. Eleven of 32 candidate gene loci studied in an Indian population replicated (p < 0.05), and 21 of 32 loci identified through previous GWAS replicated according to directionality of effect. CONCLUSIONS: This GWAS of stroke in an Indian population identified novel loci and replicated previously known loci. Genetic variants in the SUMOylation pathway, which has been implicated in brain ischemia, were identified for association with stroke.
Subject(s)
Brain Ischemia/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Stroke/genetics , Adult , Aged , Alleles , Case-Control Studies , Female , Genome-Wide Association Study , Humans , India , Male , Middle Aged , Phenotype , Quantitative Trait Loci , Risk Factors , SumoylationABSTRACT
Pulmonary cryptococcosis is likely to be misdiagnosed due to relatively non-specific clinical and radiological features. It is more frequently associated with immuno-suppressed conditions especially acquired immuno-deficiency syndrome (AIDS) and pulmonary tuberculosis (PTB). Four cases of pulmonary cryptococcosis were diagnosed over a period of eleven years. All patients in this case series were human immune-deficiency virus (HIV)-negative. The predisposing factors in these patients were diabetes mellitus (DM), acute lymphoblastic leukaemia (ALL), post-partum and pregnancy in one each of the patients. Relapse was seen in two cases. All the patients survived due to strict follow-up. Pulmonary cryptococcosis is common in non-AIDS patients and it warrants rapid diagnosis, treatment and follow-up to prevent relapse.
Subject(s)
Cryptococcosis/diagnosis , HIV Seronegativity , Lung Diseases, Fungal/diagnosis , Adult , Antifungal Agents/therapeutic use , Causality , Child , Cryptococcosis/drug therapy , Cryptococcosis/etiology , Cryptococcosis/microbiology , Diabetes Complications , Female , Follow-Up Studies , Humans , India , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/etiology , Lung Diseases, Fungal/microbiology , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/drug therapy , Puerperal Infection/diagnosis , Recurrence , Time Factors , Young AdultABSTRACT
Spontaneous intracranial hypotension (SIH) is a cause of new persistent headache, which disappears on recumbence and reappears in sitting/standing position (orthostatic headache). We present a case of orthostatic headache, where the patient was suspected to have SIH and was subjected to radionuclide cisternography (RNC) using 99m Technetium Diethylenetriaminepenta acetic acid for confirmation of diagnosis. After due consent from the patient, the radiotracer was injected intra-thecally and serial images were acquired until 24 h. The direct and indirect evidences of Cerebrospinal fluid (CSF) leakage, which were revealed in our study, provided objective evidence to the clinical diagnosis. RNC is an important investigation in diagnosing SIH and also identifying the site of CSF leak, which may aid the management.
