The study genotyped 105 hypertensives and 192 controls from a Mumbai clinic. ACE genotype distributions were nearly identical between groups (I/I 34.28% vs 34.89%; I/D 42.86% vs 42.18%; D/D 22.85% vs 22.91%), with D allele frequency exactly 0.44 in both. AT1R A/C was lower in hypertensives (13.33% vs 17.18%); no C/C genotype was observed .
The sole positive signal: D allele enriched in early-onset (β€40y) hypertensives (0.58 vs 0.39 late onset; OR 2.22, 95% CI 1.2β4.05, P<0.01) .
Strengths: Transparent methods (DMSO added to reduce I/D mistyping; mismatch PCR-RFLP for AT1R) and genotype-validating ACE activity data (I/I 21.1, I/D 36.4, D/D 49.3 IU/L in controls) .
Weaknesses: Small sample limits power, especially for the rare AT1R C allele (14 A/C cases); medicated cases confound BP analysis; no multiple-comparison correction across gender/family-history/onset subgroups makes the early-onset D allele signal vulnerable to subgroup fishing. Later Indian studies conflict: a North Indian study found significant ACE differences in cases (DD 13.04%, ID 60.14%, II 26.82%) , and an Odisha study found DD enriched in female hypertensives , suggesting the null result reflects limited power rather than definitive absence of effect.
Verdict: A careful but underpowered candidate-gene study; the early-onset D allele signal is exploratory. A well-powered stratified Indian cohort confirming or refuting D alleleβearly onset association would change this conclusion.
Author reviews: Dr T.F. Ashavaid Β· Dr K.K. Shalia Β· Dr K.G. Nair Β· Dr J.J. Dalal
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