Version 1
: Received: 21 August 2023 / Approved: 21 August 2023 / Online: 22 August 2023 (02:34:34 CEST)
How to cite:
Zahid, M.; Saif, R.; Younus, A.; Ghulam Hussain, M.; Jabeen, S.; Younas, H. Genetic Association of UMOD Gene Variant (16:20353266A>G) and Bioinformatics Analyses of the Uromodulin Protein in CKD Patients of Pakistani Origin. Preprints2023, 2023081446. https://doi.org/10.20944/preprints202308.1446.v1
Zahid, M.; Saif, R.; Younus, A.; Ghulam Hussain, M.; Jabeen, S.; Younas, H. Genetic Association of UMOD Gene Variant (16:20353266A>G) and Bioinformatics Analyses of the Uromodulin Protein in CKD Patients of Pakistani Origin. Preprints 2023, 2023081446. https://doi.org/10.20944/preprints202308.1446.v1
Zahid, M.; Saif, R.; Younus, A.; Ghulam Hussain, M.; Jabeen, S.; Younas, H. Genetic Association of UMOD Gene Variant (16:20353266A>G) and Bioinformatics Analyses of the Uromodulin Protein in CKD Patients of Pakistani Origin. Preprints2023, 2023081446. https://doi.org/10.20944/preprints202308.1446.v1
APA Style
Zahid, M., Saif, R., Younus, A., Ghulam Hussain, M., Jabeen, S., & Younas, H. (2023). Genetic Association of <em>UMOD</em> Gene Variant (16:20353266A>G) and Bioinformatics Analyses of the Uromodulin Protein in CKD Patients of Pakistani Origin. Preprints. https://doi.org/10.20944/preprints202308.1446.v1
Chicago/Turabian Style
Zahid, M., Sadia Jabeen and Hooria Younas. 2023 "Genetic Association of <em>UMOD</em> Gene Variant (16:20353266A>G) and Bioinformatics Analyses of the Uromodulin Protein in CKD Patients of Pakistani Origin" Preprints. https://doi.org/10.20944/preprints202308.1446.v1
Abstract
Chronic Kidney Disease (CKD) is one of the worldwide health threats, kidneys may be affected by internal pathologies and environmental factors as well as a number of genes are also involved in the kidney dysfunctioning, so UMOD is one of these genes which has significant effect in regulating urea and creatinine level in blood and decreased excretion of uric acid which causes interstitial damages in kidney and may result CKD. Hence, the present study is envisaged to observe the association of this gene locus (r.1264T>C) with CKD in Pakistani population using ARMS-PCR genotyping, for the purpose, a total of 75 samples were investigated, out of which 45 were found homozygous wild-type, 21 heterozygous and 09 homozygous mutants. PLINK data analysis toolset showed that our sampled population does not obeys Hardy-Weinberg Equilibrium by χ2 (2, N = 75) = 18.87, p = and Chi-square statistics with p = 1.40×10-005 showing a significant genotypic association with the subject phenotype with an alternative allele frequency of 0.15 and 0.48 within cases & controls respectively. Furthermore, an odds-ratio of 0.2 predicts that the risk of wild-type allele (A) is 0.8 times higher in patient as compared to controls and mutant allele is 0.2 times preventive in patients. Additionally, a few bioinformatics tools e.g., ProtParam, PsiPred, TMHMM-2.0, Motif Scan, ScanProsite, NetPhos3.1, GPS PAIL2.0, NetOGlyc4.0, PRmePRed, PDB-RCSB and STRING were applied to predict different characteristics of Uromodulin protein including physicochemical properties, secondary/transmembrane structures, protein conserved domains and posttranslational modifications respectively. This pilot scale study provided a comprehensive insight of the association of aforementioned genetic variant with CKD to identify and evaluate the genetic risk factors along with functional effects of the subject variant which may be used as CKD prevention by adopting DNA screening and genetic counselling recommendations.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The commenter has declared there is no conflict of interests.
Comment:
Please be aware that the PDB is a database of experimentally derived structures, not a 3D structure prediction tool! In this specific case, what you are showing in Figure 10 is a cryo-EM model of UMOD rather than a computational model. There are three relevant publications where this information is described into detail:
Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH https://pubmed.ncbi.nlm.nih.gov/35273390
PDB IDs 7PFP, 7Q3N
Commenter:
The commenter has declared there is no conflict of interests.
Cryo-EM structure of native human uromodulin, a zona pellucida module polymer
https://pubmed.ncbi.nlm.nih.gov/33196145 PDB IDs 6TQK, 6TQL
The cryo-EM structure of the human uromodulin filament core reveals a unique assembly mechanism
https://pubmed.ncbi.nlm.nih.gov/32815518 PDB IDs 6ZS5, 6ZYA
Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH
https://pubmed.ncbi.nlm.nih.gov/35273390 PDB IDs 7PFP, 7Q3N