Genetic role of CYP4A11 polymorphisms in the risk of developing cardiovascular and cerebrovascular diseases

Background: We are interested in comprehensively evaluating the potential genetic influence of rs9332978 A/G, rs1126742 T/C, and rs9333025 G/A polymorphisms of CYP4A11 (cytochrome P450 family 4, subfamily A, member 11) in the risk of developing cardiovascular and cerebrovascular diseases.

Methods: A meta-analysis was carried out using articles obtained from online databases and Stata/SE 12.0 software. We primarily used a P value of association test (P_association ) and odds ratios (OR) to assess the genetic relationships.

Results: We included 22 eligible case-control articles for our meta-analysis. For the overall meta-analysis of the rs9332978 A/G polymorphism, there was an increased risk of cardiovascular and cerebrovascular diseases in cases under the models of allele G vs. A (P_association = 0.001, OR = 1.16), AG vs. AA (P_association < 0.001, OR = 1.22), and AG+GG vs. AA (P_association < 0.001, OR = 1.22) compared with the controls. There were similar results in the subgroup analysis of "hypertension" (P_association = 0.024 for the allele model; P_association = 0.003 for the heterozygote model; and P_association = 0.005 for the dominant model). For rs1126742, there was a significant difference between cases and controls in the overall meta-analysis and subgroup of "Caucasian," "hypertension," and "population-based (PB)" under all of the genetic models (all P_association < 0.05, OR > 1). Furthermore, a decreased risk was detected in the overall and "PB" subgroup meta-analysis of rs9333025 under the models of A vs. G, AA vs. GG, and AA vs. GG+GA (all P_association < 0.05, OR < 1).

Conclusion: The rs1126742 T/C polymorphism of CYP4A11 is more likely to be a genetic risk factor for the hypertension cases in the Caucasian population. Moreover, whereas the AG genotype of CYP4A11 rs9332978 may be associated with an increased risk of hypertension, the AA genotype of rs9333025 may be linked to a decreased risk of cardiovascular and cerebrovascular diseases.