Generation and characterization of human-derived induced pluripotent stem cell line (IGIBi010-A) from a patient with neurodegenerative disease phenotype carrying mutation in SQSTM1/p62 gene.

SQSTM1 (Sequestosome 1) also known as p62, plays several important physiological roles in the cell. It regulates autophagy and mitochondrial homeostasis and can further lead to metabolic reprogramming. Pathogenic variants in SQSTM1 gene are known to cause Neurodegeneration with ataxia, dystonia, and gaze palsy in autosomal recessive inheritance fashion. We report here, the generation of induced pluripotent stem cell (iPSC) line (IGIBi010-A) carrying a novel homozygous frameshift variant in SQSTM1 i.e. p.Leu251SerfsTer4. In future, this iPSC line will be used as a resource to elucidate the molecular pathway, targeting strategies for disease biology derived by variation in SQSTM1 gene.

Generation and characterization of two human iPSC lines, IGIBi014-A and IGIBi015-A, from Friedreich's ataxia (FRDA) patients with pathogenic (GAA/TTC)n repeat expansion in first intron of the Frataxin (FXN) gene.

Friedreich's ataxia (FRDA) is a rare neurodegenerativedisorder caused by over expansion of GAA repeats in thefirstintron ofFXN gene. Here, we generated two iPSC lines from FRDA patients with biallelic expansion of GAA repeats in the first intron ofFXNgene.IGIBi014-A and IGIBi015-Aboth iPSC lines demonstrated characteristics of pluripotency, normal karyotypes (46, XY),the capacity to differentiate into all three germ layers, and the ability to sustain the GAA repeat expansion with decreased FXN mRNA expression. These cell lines will be utilized to comprehend the pathophysiology of the illness and the FRDA's predictive phenotypes.

Generation and characterization of iPSC lines from Friedreich's ataxia patient (FRDA) with GAA.TTC repeat expansion in the Frataxin (FXN) gene's first intron (IGIBi016-A) and a non-FRDA healthy control individual (IGIBi017-A).

Friedreich's ataxia is a spinocerebellar degenerative disease caused by microsatellite (GAA.TTC)n repeat expansion in the first intron of FXN gene. Here, we developed iPSC lines from an FRDA patient (IGIBi016-A) and non-FRDA healthy control (IGIBi017-A). Both iPSC lines displayed typical iPSC morphology, expression of pluripotency markers, regular karyotypes (46, XY; 46, XX), capacity to grow into three germ layers, and FRDA hallmark -GAA repeat expansion and decreased FXN mRNA. Through these iPSC lines, FRDA phenotypes may be replicated in the in vitro assays, by creating neuron subtypes, cardiomyocytes and 3D organoids, for molecular and cellular biomarkers and therapeutic applications.

Association between interleukin-6 (G174C and C572G) promoter gene polymorphisms and risk of ischemic stroke in North Indian population: a case-control study.

BACKGROUND: Polymorphisms of G174C and C572G in the interleukin-6 (IL-6) promoter gene can affect both transcription and secretion of IL-6 and may be involved in inflammation related to and pathogenesis of ischemic stroke (IS). Whether these IL-6 gene polymorphisms are risk factors for IS or not, remains controversial. OBJECTIVE: The aim of this study was to determine the association between IL-6 G174C and C572G gene polymorphisms and susceptibility to ischemic stroke in North Indian Population. METHODS: Two hundred and fifty IS patients and 250 age- and sex-matched controls were studied. Genotyping was performed using SNaPshot method. Stroke was classified using Trial of Org 10172 in acute stroke treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between IL-6 (G174C and C572G) polymorphisms and risk of IS. RESULTS: Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary life style and low socioeconomic status were found to be associated with the risk of IS. Conditional logistic regression analysis showed a significant association of IL-6 G174C with the risk of IS under dominant model (OR, 1.61; 95%CI, 1.0-2.4; P value 0.02) and allelic model (OR, 1.5; 95%CI, 1.0-2.1; P value 0.02). For IL-6 C572G, multivariate adjusted analysis showed a significant association with the risk of IS under dominant model for overall IS (OR, 1.81; 95%CI, 1.04-3.15; P value 0.03) and small vessel disease subtype of IS (OR, 2.8; 95%CI, 1.3-6.0; P value 0.006). CONCLUSION: Our results suggest that IL-6 (G174C) polymorphism is significantly associated with the risk of IS in North Indian population. However, IL-6 (C572G) polymorphism is found significantly associated with the risk of IS after adjusting the demographic and risk factors variables. Prospective studies with large sample size are required for independent validation. Our findings could be helpful in identifying individuals at increased risk for developing IS.