Search bioRxiv⌕ Search

Biology subjects

Hussain, M. G.

Publications and source records attributed to Hussain, M. G..

2 recordsLinked to original sources
bioRxiv2023

Genetic Association of CYP1A2 Gene Variant (rs762551) with Caffeine Induced-Hypertension Susceptibility and Cytochrome P450 1A2 Protein Analyses

High blood pressure is one of the most common illnesses affecting the Pakistani population due to, but not limited to, dietary habits, sedentary lifestyle and socio-economic aspects which have devastating effects on human health and general well-being. Caffeine is metabolized by CYP1A2 which results in lowered blood pressure while its retention in case of low metabolism may lead to hypertension. This phenomenon occurs because caffeine and its metabolites block A1 receptors in the kidney lowering the function of adenosine in blood pressure regulation. Current research aimed to demonstrate the genetic association of CYP1A2 gene variant 15:74749576C>A (C allele lowering CYP1A2 activity) within caffeine induced hypertensive individuals of Pakistani origin using ARMS-PCR. This pilot scale study revealed that overall, 8%, 56% and 36% sampled population (n=50) is homozygous wild-type (C/C), heterozygous (C/A) and homozygous mutant (A/A) respectively. Similarly, alternative allele frequency is 0.28 and 0.48 in cases and controls. Chi-square ({chi}2) association test using PLINK data analysis toolset was applied which showed significant results of {chi}2(2, N = 50) = 4.244, p = 0.039. Hardy Weinberg Equilibrium analysis was also applied which establishes that sampled population is obeying the principle with p-value of 0.241. Moreover, odds-ratio depicts that the mutant allele is 0.42 times less prevalent in cases vs. controls. A few bioinformatics tools were employed e.g., ProtParam, PsiPred, PDB-RCSB, Motif finder, CTU-TMHMM-2.0, ScanProsite, GPS PAIL2.0, PRmePRed, NetOGlyc4.0, NetPhos3, SIFT analysis and STRING database in order to predict physicochemical properties, secondary structure, 3-dimensional structure, conserved motifs, transmembrane structure, post-translational modifications, protein variants impact on its function and protein-protein interactions respectively. The current endeavor attempted to provide the genetic architecture of the aforementioned variant in this case-control study in Pakistani individuals, which can pave paths of preventive medicine initiatives through genetic counsel of the masses.

genetics↗
bioRxiv2023

Genetic Association of SLC47A1 Gene Variant (17:19571562C >T) and Bioinformatics Analyses of MATE1 Protein in Chronic Kidney Disease Patients of Pakistani Origin

Chronic Kidney Disease (CKD) is a serious human threat worldwide which is associated with a number of environmental, clinical and genetic factors that affect serum creatinine (SCr) and glomerular filtration rate (eGFR). One of the best biochemical and genetic markers to study renal functioning is SLC47A1 which encodes MATE1 protein and can be a promising target to study its genetic causes, subject protein is a cationic transporter involved in the regulation of creatinine and urea levels in the blood which may cause toxicity and renal disorders. Hence, the current study focused to interrogate the putative association of SLC47A1 gene variant (17:19571562C>T) in 75 individuals (cases=50, controls=25) of Pakistani origin using ARMS-PCR genotyping, out of which 10 were found heterozygous, 57 homozygous wild-type and 08 homozygous mutants. PLINK data analysis toolset was used which manifested that sampled population complies the Hardy-Weinberg Equilibrium by {chi}2 (2, N = 75) =, p = 4.756 x 10-005, similarly the Chi-square statistics p = 0.03274 along with odds-ratio of 3.244 showing a significant genotypic association with the subject phenotype indicating that mutant allele is almost 3-times more prevalent in cases vs control cohorts with an alternative allele frequency of 0.22 and 0.08 in CKD patients and healthy controls respectively. Besides, few of the bioinformatics tools i.e., ProtParam, PsiPred, PDB-RCSB, Motif Scan, CTU-TMHMM-2.0, ScanProsite, PRmePRed, GPS PAIL2.0, NetOGlyc4.0, NetPhos3, SIFT, Polyphen-2 and STRING were also used for the prediction of different parameters of both the wild-type and mutant MATE1 proteins such as physiochemical properties, secondary structure prediction, 3-D structure, protein conserved domains, transmembrane structures, posttranslational modifications, SNP prediction/amino acid substitution, pathogenicity and protein-protein interaction networks. Current preliminary genotyping provided an insight into the association of the aforementioned genetic variant with CKD to estimate the genetic risks along with prediction of its functional effects in the system biology context which may be considered for developing new targeted drugs along with genetic counselling initiatives to evade this peril in the population.

genetics↗