Genetic association of APOA1 rs670 and rs5069 variants with the risk of developing cardiovascular disease: A systematic review and meta‑analysis

Apolipoprotein A1 (APOA1) is a major component of high‑density lipoprotein and plays a critical role in lipid metabolism and cardiovascular prevention. Genetic variations in APOA1, including rs670 (‑75 G>A) and rs5069 (+83 C>T), have been investigated for their association with the risk of developing cardiovascular disease (CVD). The present systematic review and meta‑analysis evaluated the associations of APOA1 rs670 and rs5069 polymorphisms with the risk of developing CVD. For this purpose, a systematic literature search was conducted to identify eligible case control studies evaluating APOA1 rs670 and rs5069 polymorphisms and the risk of developing CVD. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled under allele contrast, dominant, recessive and over dominant genetics models using random effects meta‑analyses. Between‑study heterogeneity was assessed using Cochran's Q test and the I2 statistics. Study quality was evaluated using the Newcastle‑Ottawa Scale. Sensitivity analysis was performed using the leave‑one‑out approach, and publication bias was evaluated using funnel plots. A total of ten studies were included in the analysis, with five studies each for rs670 and rs5069. The primary pooled analysis revealed no significant association between either the APOA1 rs670 or rs5069 polymorphisms and the risk of developing CVD under any genetic model. Substantial heterogeneity was detected across studies. Leave‑one‑out sensitivity analysis confirmed the stability of the pooled estimates. Hardy‑Weinberg equilibrium (HWE)‑based sensitivity analysis for rs670 revealed a significant association under the allele contrast (OR, 1.81; 95% CI, 1.18‑2.75; P=0.005) and dominant models (OR, 1.75; 95% CI, 1.17‑2.62; P=0.006) after excluding studies deviating from the HWE, whereas a similar analysis for rs5069 was not feasible as only one HWE compliant study remained. On the whole, the primary pooled analysis found no significant association between the APOA1 rs670 or rs5069 polymorphisms and susceptibility to CVD. However, HWE‑based sensitivity analysis suggests that HWE deviation may influence the observed association for rs670. Further large‑scale studies involving diverse populations are required to validate these findings.