Background <p>Angiotensin-Converting Enzyme 2 (ACE2) is a key enzyme in the renin–angiotensin–aldosterone system (RAAS). Hence, genetic variants within ACE2 can influence individual susceptibility to hypertension. This study investigates the association of rs2285666 and rs879922 within ACE2 with hypertension in Bangladeshi population.</p> Methods and results <p>In this cross-sectional case-control study, the genotypic and allelic frequencies of rs2285666 and rs879922 were determined in 351 individuals (Normotensive = 161, Hypertensive = 190) using PCR-RFLP. Univariate and multivariate logistic regression analyses were conducted to investigate the association of genotypic distributions of these variants with hypertension. The T allele of rs2285666 was found to be significantly associated with hypertension in male participants after adjusting for age and BMI [OR^a (95%CI): 2.04 (1.10–3.83), p^a: 0.03]. The genotypic analysis revealed no significant association of T and G allele of rs2285666 and rs879922, respectively with hypertension in any of the genetic inheritance models with or without adjusting for confounders in female participants. Neither rs2285666 nor rs879922 showed significant associations with systolic or diastolic blood pressure levels in hypertensive males or females after adjustment for age, BMI, and antihypertensive drug treatment. The two SNPs exhibited weak linkage disequilibrium (LD) and haplotype analysis revealed no significant association with hypertension.</p> Conclusion <p>In conclusion, we found that rs2285666 shows a gender-specific association with hypertension, whereby the T allele increases hypertension susceptibility in males. However, these findings should be confirmed in larger cohorts and across diverse populations to ensure a more robust evaluation.</p>