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.