Association of ACE I/D polymorphism with essential hypertension in South-Asian populations: Gender-bias in Indian populations—evidence from case-control and meta-analysis studies

Introduction The role of Angiotensin Converting Enzyme (ACE) intron-16 I/D polymorphism (rs4646994) in essential hypertension (EH) is contradictory in South Asian populations. The study objectives were to investigate correlation between rs4646994 polymorphism and EH in the North-Indian population of Jammu, and to perform a meta-analysis to validate its role in South-Asian populations. Methodology A total of 422-cases and 395-controls were genotyped in the original study. Meta-analysis was performed on 4987-cases and 5302-controls following the PRISMA and STREGA guidelines. SPSS-v25.0 and web-based tools were used for statistical analyses. Results Our original case-control study revealed a statistically significant association between the rs4646994 polymorphism and EH, with the D allele being the risk allele. The observed significance level was higher when the recessive genetic model was tested [OR = 1.68(95%CI:1.16–2.43), P = 0.006 ]. Interestingly, only males carrying the DD-genotype were at significantly higher odds of developing EH [OR = 2.68(95%CI:1.58–4.53), P < 0.0001 ]. The meta-analysis further corroborated an increased risk for EH in the presence of DD-genotype in the South-Asian populations [OR = 1.48(95%CI:1.35–1.62), P < 0.0001 ] and largely supported the gender-wise differences in Indian populations, with males at relatively higher risk. Conclusion Our data provide strong evidence supporting the role of rs4646994 polymorphism in essential hypertension in the South-Asian populations, particularly Indians, and highlight the significance of considering gender as a biological variable in genetic studies related to hypertension risk.