Browsing by Author "Sheikh Nizamuddin"

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Common variant c.-22 + 155C > T of BDNF as a genetic risk factor of opium addiction
(Elsevier B.V., 2022) Anit Kumar; Sheikh Nizamuddin; Niraj Rai; Biswajit Roy; Manju Kashyap; Gaurav Gupta; Vineet Kaswan; Naveen Kumar Kaushik; Jatin Bodwal; Poonam Rana; Anshuman Mishra; Gyaneshwer Chaubey; H.T. Marc Timmers; Kumarasamy Thangaraj; Amit Kaushik
Opioid use disorder is largely genetic in nature. The common genetic variants present in population might be modulating the risk by affecting expression level of genes in the brain. Here, we study common variants in promoter region of brain-derived neurotrophic factor (BDNF) and Dopamine receptor D2 (DRD2) in a highly prevalent opium addiction geographical region. We identify highly expressed isoforms using CAGE datasets and its associated promoter. Common variants were extracted from promoters and genotyped in addicts compared to controls. The associated variants obtained through hitchhiking events were removed and eQTL analysis was performed. We identified two mutations (rs7944119:G > T and rs13306221:C > T) in the promoter of BDNF to be significantly associated with the addiction. In the dominant inheritance model, both rs7944119 and rs13306221 increases the risk of addiction. Of these two, rs7944119 was in linkage disequilibrium with rs13306221 and showed association due to hitchhiking. The rs13306221-T was associated with a lower expression level of the short BDNF isoform in the Cerebellar cortex. This finding suggests that rs13306221 (c.-22 + 155C > T) could increase risk of addiction by decreasing the expression level of the short isoform of BDNF, therefore, changes in the expression of the BDNF might not be the effect, but rather a cause of opium addiction disorder. Or, subjects with less expression of BDNF are more prone to addiction and addiction further decreases expression of BDNF short isoform in the brain. Although, it should be explored further in more detail. © 2022 Elsevier B.V.
Variations in macrophage migration inhibitory factor gene are not associated with visceral leishmaniasis in India
(Elsevier Ltd, 2019) Anshuman Mishra; Pandarisamy Sundaravadivel; Sunil Kumar Tripathi; Rajan Kumar Jha; Jaydeep Badrukhiya; Nipa Basak; Isha Anerao; Akshay Sharma; Ajayi Ebenezer Idowu; Abhishek Mishra; Sonika Pandey; Umesh Kumar; Sakshi Singh; Sheikh Nizamuddin; Nitin C Tupperwar; Aditya Nath Jha; Kumarasamy Thangaraj
Background: The host genetic factors play important role in determining the outcome of visceral leishmaniasis (VL). Macrophage migration inhibitory factor (MIF) is an important host cytokine, which is a key regulator of innate immune system. Genetic variants in MIF gene have been found to be associated with several inflammatory and infectious diseases. Role of MIF is well documented in leishmaniasis diseases, including Indian visceral leishmaniasis, where elevated level of serum MIF has been associated with VL phenotypes. However, there was no genetic study to correlate MIF variants in VL, therefore, we aimed to study the possible association of three reported MIF gene variants −794 CATT, −173G > C and non-coding RNA gene LOC284889 in Indian VL phenotype. Methods: Study subjects comprised of 214 VL patients along with ethnically and demographically matched 220 controls from VL endemic regions of Bihar state in India. Results: We found no significant difference between cases and controls in allelic, genotypic and haplotype frequency of the markers analysed [-794 CATT repeats (χ2 = 0.86; p = 0.35; OR = 0.85; 95% CI = 0.61–1.19); −173 G > C polymorphism (χ2 = 1.11; p = 0.29; OR = 0.83; 95% CI = 0.59–1.16); and LOC284889 (χ2 = 0.78; p = 0.37; OR = 0.86; 95% CI = 0.61–1.20)]. Conclusion: Since we did not find any significant differences between case and control groups, we conclude that sequencing of complete MIF gene and extensive study on innate and adaptive immunity genes may help in identifying genetic variations that are associated with VL susceptibility/resistance among Indians. © 2018 The Authors