Genetic Association of CYP1A2 Variant (rs762551) with Caffeine Induced-Hypertension Susceptibility and Subject Protein Analyses

CYP1A2 rs762551 and Caffeine-Induced Hypertension

Abstract

Hypertension affects a large proportion of Pakistan’s population, with prevalence above 46% in both urban and rural areas. Caffeine has multiple cardiovascular effects. Acutely, adenosine receptor antagonism can increase blood pressure, but chronic consumption might prevent it. CYP1A2, a liver enzyme responsible for metabolizing more than 95% of caffeine by demethylation, has genetic variability, with the rs762551 variant (-163 C>A) affecting activity. Objectives: To investigate the association between the rs762551 variant and caffeine-induced hypertension susceptibility in a Pakistani population, and summarize important features of the CYP1A2 protein. Methods: A case-control genotyping study was conducted with 48 participants, including 24 hypertensive and 24 controls. Genomic DNA was extracted and genotyped by ARMS-PCR. The Hardy-Weinberg Equilibrium (HWE) was calculated using chi-square and odds ratio with 95% CI. An in-silico study was also conducted to examine the structure and function of CYP1A2 protein. Results: Genotypic frequencies within cases: 11 (AA), 12 (AC), and 1 (CC), controls: 5 (AA), 16 (AC), and 3 (CC). Allele frequencies within cases: A=0.71 and C=0.29, and in controls: A=0.54 and C=0.46. HWE (χ²=2.82, p=0.093). The C‑allele was not significantly associated with hypertension (OR=0.49, 95 % CI 0.21–1.13; χ²=2.18, p=0.14). In-silico studies confirmed that the CYP1A2 gene encodes a microsomal liver enzyme involved in caffeine demethylation. Conclusions: No significant association between the CYP1A2 rs762551 was found in this cohort. More extensive studies, including lifestyle data, are needed to understand gene-environment interactions.