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In this study, we sought to examine the association between 10 genetic variants in the matrix metalloproteinase (MMP) family genes and the risk of hypertension among northeastern Han Chinese. This was a hospital-based case-control study involving 1009 sporadic hypertensive patients and 756 age-, gender- and ethnicity-matched normotensive controls. The genotypes of the 10 examined variants were determined by PCR-ligase detection reaction method. The genotype/allele distributions of rs3025058 and rs679620 differed significantly between patients and controls, with a Bonferroni corrected α of 0.05/10. The probability of having hypertension was significant for rs3025058 under the additive (odds ratio; 95% confidence interval; P: 1.33; 1.16-1.53; &lt;0.001) and dominant (1.43; 1.18-1.73; &lt;0.001) models and was significant for rs679620 under the additive (1.27; 1.1-1.46; &lt;0.001) model after adjusting for confounders. In a combined analysis, when compared with the reference group (score&lt;3.5 for unfavorable genotypes), participants in the medium- and high-risk groups had odds ratios that increased to 1.61 (95% CI: 1.25-2.51; P&lt;0.001) and 1.92 (95% CI: 1.54-2.39; P&lt;0.001) after adjustment, respectively. Interaction analysis showed that a three-locus model including rs3025058, rs679620 and rs243865 was the best, with a maximum testing accuracy of 0.6605 and a cross-validation consistency of 10 (P=0.0022). Taken together, our findings suggest that the true association between individual variants and the risk of hypertension may not be revealed until combined analyses of multiple variants from genes involving a specific physiological or cellular function are performed. Moreover, we propose a three-locus model that can best characterize the genetic interactions of the MMP multiple gene family.

Genetic variants of the matrix metalloproteinase family genes and risk for hypertension: a case–control study among northeastern Han Chinese