Angiotensin-converting enzyme insertion/deletion polymorphism and accumulation of cardiometabolic and endocrine conditions among community-recruited adults in eastern Algeria

The accumulation of chronic conditions may reflect shared biological susceptibility. We assessed whether the angiotensin-converting enzyme insertion/deletion polymorphism was associated with four prespecified, participant-reported, physician-diagnosed conditions. This multisite crosssectional study included 544 adults consecutively recruited from community settings across eight wilayas in Eastern Algeria. Multimorbidity was defined as at least two of the following conditions: hypertension, diabetes, thyroid dysfunction, and cardiac disease. Logistic regression was adjusted for age, sex, and tobacco use. Among the 544 participants, 84 (15.4%) had multimorbidity. Genotype was a significant contributor to the adjusted model (likelihood-ratio P=0.037). Compared with the deletion/deletion (DD) genotype, the insertion/deletion (ID) genotype was associated with higher odds of multimorbidity (adjusted odds ratio, 2.15; 95% confidence interval, 1.19-3.90; P=0.011), whereas the estimate for the insertion/insertion (II) genotype was imprecise and not statistically significant (adjusted odds ratio, 0.74; 95% confidence interval, 0.20-2.77; P=0.656). The ID genotype was associated with the presence of at least two conditions but not with exactly one condition, and no additive association with the D allele was detected. Genotype frequencies deviated from Hardy– Weinberg equilibrium (exact P=2.53 × 10^{-7} ), reflecting a heterozygote deficit. Bias analysis indicated that non-differential misclassification of heterozygotes as DD would attenuate the observed association. These findings suggest an association between the ID genotype and multimorbidity, although they should be interpreted cautiously and confirmed in independent studies.