Association of Polymorphisms in the Atrial Natriuretic Factor Gene with the Risk of Essential Hypertension: A Systematic Review and Meta-Analysis

Background: Studies evaluating the association between the atrial natriuretic peptide (ANP) genetic polymorphism and the risk of essential hypertension (EH) have reported inconsistent results. The aim of this meta-analysis was to provide a more reliable estimation of the possible relationship between the atrial natriuretic peptide genetic polymorphism and the risk of essential hypertension (EH). Methods: Relevant articles were searched to identify all case-control or cohort design studies of the associations between ANP polymorphism and EH. The heterogeneity was checked using the Q test and the inconsistent index (I-2). The odds ratio (OR) test and 95% confidence interval (CI) were calculated in a fixed or random effects model to evaluate the strength of association. Begg's test and Egger's test were applied to evaluate the publication bias. Results: A total of 25 case-control studies including 5520 cases and 5210 controls exploring the association between ANP polymorphism and EH were available for this meta-analysis. No significant association between the T2238C polymorphism and overall EH risk under the five genetic models was found (C vs. T: OR = 1.1, 95%CI = 0.94-1.2, p = 0.38; TC vs. TT: OR = 1.1, 95%CI = 0.88-1.5, p = 0.32; CC vs. TT: OR = 1.3, 95%CI = 0.90-1.9, p = 0.16; (CC + TC) vs. TT: OR = 1.1, 95%CI = 0.88-1.4, p = 0.35; CC vs. (TT + TC): OR = 1.1, 95%CI = 0.83-1.4, p = 0.55). We also found that the G1837A polymorphism had no significant association with overall EH risk (A vs. G: OR = 1.3, 95%CI = 0.96-1.9, p = 0.090; GA vs. GG: OR = 1.5, 95%CI = 0.83-2.6, p = 0.19; AA vs. GG: OR = 0.87, 95%CI = 0.34-2.3, p = 0.78; (AA + GA) vs. GG: OR = 1.5, 95%CI = 0.86-2.5, p = 0.17; AA vs. (GG + GA): OR = 1.3, 95%CI = 0.85-2.0, p = 0.22). In the analysis of the T1766C polymorphism, after removing the study of Nkeh, the 1766C allele suggested a protective effect in the model of TC vs. TT (OR = 0.64, 95%CI = 0.47-0.86, p = 0.003) and (CC + TC) vs. TT (OR = 0.64, 95%CI = 0.48-0.87, p = 0.004). Conclusions: This meta-analysis suggested that no significant relationships between ANP T2238C, G1837A gene polymorphisms and the risk of essential hypertension exist. Conversely, the ANP T1766C gene polymorphism may be associated with the risk of essential hypertension, and the 1766C allele may be a protective factor against EH. However, due to the number of limited articles on the T1766C polymorphisms, further studies are still needed to accurately prove the association between the T1766C gene polymorphism and the risk of essential hypertension.