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

Abstract

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; <0.001) and dominant (1.43; 1.18-1.73; <0.001) models and was significant for rs679620 under the additive (1.27; 1.1-1.46; <0.001) model after adjusting for confounders. In a combined analysis, when compared with the reference group (score<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<0.001) and 1.92 (95% CI: 1.54-2.39; P<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.