Showing papers by "Moinak Banerjee published in 2020"
TL;DR: This work proposes three potentially important genetic gateways to COVID‐19 infection, which could explain at least in part the discrepancies of its spread, severity, and mortality.
Abstract: The dynamics, such as transmission, spatial epidemiology, and clinical course of Coronavirus Disease-2019 (COVID-19) have emerged as the most intriguing features and remain incompletely understood. The genetic landscape of an individual in particular, and a population in general seems to play a pivotal role in shaping the above COVID-19 dynamics. Considering the implications of host genes in the entry and replication of SARS-CoV-2 and in mounting the host immune response, it appears that multiple genes might be crucially involved in the above processes. Herein, we propose three potentially important genetic gateways to COVID-19 infection; these could explain at least in part the discrepancies of its spread, severity, and mortality. The variations within Angiotensin-converting enzyme 2 (ACE2) gene might constitute the first genetic gateway, influencing the spatial transmission dynamics of COVID-19. The Human Leukocyte Antigen locus, a master regulator of immunity against infection seems to be crucial in influencing susceptibility and severity of COVID-19 and can be the second genetic gateway. The genes regulating Toll-like receptor and complement pathways and subsequently cytokine storm induced exaggerated inflammatory pathways seem to underlie the severity of COVID-19, and such genes might represent the third genetic gateway. Host-pathogen interaction is a complex event and some additional genes might also contribute to the dynamics of COVID-19. Overall, these three genetic gateways proposed here might be the critical host determinants governing the risk, severity, and outcome of COVID-19. Genetic variations within these gateways could be key in influencing geographical discrepancies of COVID-19.
110 citations
TL;DR: High-resolution intracranial vessel wall imaging characteristics of concentric wall thickening and enhancement are relatively rare in a cohort of patients with Moyamoya disease and may predict future ischemic events in patients with MMD.
Abstract: BACKGROUND AND PURPOSE: Very few data are available with regard to high-resolution intracranial vessel wall imaging characteristics of Moyamoya disease and their relation to ischemic stroke risk. We investigated the high resolution imaging characteristics of MMD and its correlation with recent ischemic events. MATERIALS AND METHODS: Patients with Moyamoya disease confirmed by DSA, including patients after revascularization, were enrolled. All the patients underwent high-resolution intracranial vessel wall imaging. Vessel wall thickening, enhancement, and the remodeling index of the bilateral distal ICA and proximal MCA were noted. The patients were followed up at 3 months and 6 months after high-resolution intracranial vessel wall imaging and the association of ischemic events with imaging characteristics was assessed. RESULTS: Twenty-nine patients with Moyamoya disease were enrolled. The median age at symptom onset was 12 years (range, 1–51 years). A total of 166 steno-occlusive lesions were detected by high-resolution intracranial vessel wall imaging. Eleven lesions with concentric wall thickening (6.6%) were noted in 9 patients. Ten concentric contrast-enhancing lesions were observed in 8 patients, of which 3 patients (4 lesions) showed grade II enhancement. The presence of contrast enhancement (P = .01) and wall thickening (P ≤ .001) showed a statistically significant association with ischemic events within 3 months before and after the vessel wall imaging. Grade II enhancement showed a statistically significant (P = .02) association with ischemic events within 4 weeks of high-resolution intracranial vessel wall imaging. The mean ± standard deviation outer diameter of the distal ICA (right, −3.3 ± 0.68 mm; left, 3.4 ± 0.60 mm) and the remodeling index (right, 0.71 ± 0.13; left, 0.69 ± 0.13) were lower in Moyamoya disease. CONCLUSIONS: High-resolution intracranial vessel wall imaging characteristics of concentric wall thickening and enhancement are relatively rare in our cohort of patients with Moyamoya disease. The presence of wall thickening and enhancement may predict future ischemic events in patients with Moyamoya disease.
26 citations
TL;DR: It is concluded that increased production of pro-inflammatory cytokines and reduced production of anti- inflammatory cytokines may influence the Th1/Th2 equilibrium resulting in a triggering of Th1 mediated inflammatory responses in development of RA.
Abstract: Rheumatoid arthritis (RA) is a crucial inflammatory joint disease characterized by loss of self-tolerance and severe cartilage loss, autoimmune, and subchondral bone erosions. Cytokines are the key regulators of inflammatory responses. Homeostatic imbalances in pro- and anti-inflammatory cytokine activities can result in pathogenic inflammatory reactions. These imbalances could be initiated by environmental factors but the ability to define the threshold of environmental impact relies on the genetic background of the pro- and anti-inflammatory cytokines. To address this a case-control association study was carried out in 429 individuals from Malayalam speaking ethnic population from South India. Functionally relevant SNPs from IL-10, IL-6, IL-1β and IL-1RN were genotyped using PCR -RFLP and sequencing. Meta-analysis was performed for the associated variants of IL-10, IL-1β. Significant association with RA was observed with IL-1β rs1143634, rs1143627, IL-10 rs1800896, IL-6 rs1800796, rs1800797. The associated SNPs are likely to impact transcriptional activity of a gene. Meta-analysis with global populations also provide evidence that IL-10 and IL-1β could be a global marker for RA. The functional significance of associated risk variants of IL-1β and IL-6 indicate increased production of the pro-inflammatory cytokines while IL-10 risk allele suggest reduced production of anti- inflammatory cytokines. The study concludes that increased production of pro-inflammatory cytokines and reduced production of anti- inflammatory cytokines may influence the Th1/Th2 equilibrium resulting in a triggering of Th1 mediated inflammatory responses in development of RA.
5 citations
TL;DR: A case-control study for RNF 213 polymorphism involving 65 Moya moya disease (MMD) patients, 75 parents, and 120 controls were performed in this article, where a total of 21 polymorphisms were screened, of which 17 SNPs were monomorphic.
Abstract: Background and purpose Polymorphisms in Ring Finger Protein 213 (RNF 213) gene have been detected to confer genetic susceptibility to Moya moya disease (MMD) in the East Asian population. We investigated the frequency of RNF 213 gene polymorphism and its association with MMD phenotypes in the Indian population. Materials and methods A case-control study for RNF 213 polymorphism involving 65 MMD patients, 75 parents, and 120 controls were performed. A total of 21 SNPs were screened, of which 17 SNPs were monomorphic. Allelic and genotypic frequency of all polymorphic SNPs were assessed and its association with MMD phenotypes was evaluated. Results The median age of symptom onset was 9 (range 2–17) and 37 years (range 20–58) in paediatric and adult patients respectively. A strong association was observed with RNF 213 rs112735431(p.R4810K) and MMD. Out of 65 patients with MMD, five patients carried the homozygous risk AA genotype. None of the healthy controls carried this homozygous mutation. The mutant allele was detected in MMD patients from Tamil Nadu and North eastern states of India (p = <0.0001). All the patients carrying the mutant allele had an early age of onset (p = <0.0001), higher incidence of bilateral disease (p = <0.002), positive family history (p = 0.03), higher Suzuki angiographic stage (≥3) (p<0.0006) and recurrent neurological events (ischemic strokes and TIAs) (p = <0.009). Conclusion The homozygous rs112735431(p.R4810K) variant in RNF 213 variant not only predicts the risk for MMD but can also predict the phenotypic variants.
4 citations
TL;DR: The study demonstrates that the genetic variants in folate cycle and methionine cycle genes such as MTHFR, M TRR, MTR, BHMT and DNMT1 are associated with the risk of aneurysm and have functional relevance and are predictive of decreased expression indicative of altered methylation levels that may result in elevated homocysteine.
Abstract: Aim: Intracranial aneurysm is often asymptomatic until the time of rupture. Elevated homocysteine is reported in vascular diseases. Identifying early events in homocysteine metabolism through methylation map genes may prevent fatality. Materials & methods: In the present study, we investigated the role of variants in methylation map genes in ethnically matched 480 individuals that can influence the homocysteine levels and promote development of aneurysm. Results: The study demonstrates that the genetic variants in folate cycle and methionine cycle genes such as MTHFR, MTRR, MTR, BHMT and DNMT1 are associated with the risk of aneurysm. Conclusion: The associated allelic variants in these genes have functional relevance and are predictive of decreased expression indicative of altered methylation levels that may result in elevated homocysteine.
1 citations