Association of SUMOlation Pathway Genes With Stroke in a Genome-wide Association Study in India

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

Apolipoprotein-E genotypes and myasthenia gravis

Autoimmune myasthenia gravis (MG) is a disorder of neuromuscular junction. Possible role of multiple genes in the development of the MG has been documented. This case-control study, studied the association of apolipoprotein E (Apo-E) alleles with MG. Anti-AChR antibody was measured using radio receptor immunoassay. Apo-E genotypes were analyzed in 120 MG patients and 120 healthy subjects. Comparison between patients with MG and controls showed no significant association with Apo-E allelic variants. However, a significant association of Apo-E4 allele with AChR-antibody positive patients was observed (P = 0.007). Also, among seropositive patients, a significant association was seen between female gender and Apo-E4 allele (P = 0.023). Our results suggest that the presence of Apo-E4 allele might influence seropositive status in patients with MG and seems an associated susceptible factor in female patients

Utility of IL-6 in the Diagnosis, Treatment and Prognosis of COVID-19 Patients: A Longitudinal Study

COVID-19 has caused devastating effects worldwide ever since its origin in December 2019. IL-6 is one of the chief markers used in the management of COVID-19. We conducted a longitudinal study to investigate the role of IL-6 in diagnosis, treatment, and prognosis of COVID-19-related cytokine storm. Patients with COVID-19 who were admitted at AIIMS Rishikesh from March to December 2020 were included in the study. Patients with no baseline IL-6 value at admission and for whom clinical data were not available were excluded. Clinical and laboratory data of these patients were collected from the e-hospital portal and entered in an excel sheet. Correlation was seen with other inflammatory markers and outcomes were assessed using MS Excel 2010 and SPSS software. A total of 131 patients were included in the study. Of these, 74.8% were males, with mean age 55.03 &plusmn; 13.57 years, and mean duration from symptom onset being 6.69 &plusmn; 6.3 days. A total of 82.4% had WHO severe category COVID-19, with 46.56% having severe hypoxia at presentation and 61.8% of them having some comorbidity. Spearman rank correlation coefficient of IL-6 with D-dimer was 0.203, with LDH was &minus;0.005, with ferritin was 0.3, and with uric acid was 0.123. A total of 11 patients received Tocilizumab at a mean duration from symptom onset of 18.09 days, and 100% mortality was observed. Deaths were reported more in the group with IL-6 &ge; 40 pg/mL (57.1% vs. 40.2%, p = 0.06). ICU admissions and ventilator requirement were higher in the IL-6 &ge; 40 pg/mL group (95.9% vs. 91.4%, p = 0.32 and 55.1% vs. 37.8%, p = 0.05). The study showed that IL-6 can be used as a possible &ldquo;thrombotic cytokine marker&rdquo;. Higher values of IL-6 (&ge;40 pg/mL) are associated with more deaths, ICU admissions, and ventilator requirement