Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.
Clin Chim Acta. 2010 Dec 14;411(23-24):1940-4. doi: 10.1016/j.cca.2010.08.008. Epub 2010 Aug 11.
Matrix metalloproteinases (MMPs) are involved in cardiac remodeling and are encoded by genes showing genetic polymorphisms that have functional implications. We examined whether MMP-9 genetic polymorphisms are associated with hypertension and with left ventricular (LV) remodeling in hypertensive patients.
We studied 173 hypertensive patients and 137 age, race and gender matched healthy controls. Heart echocardiography was performed in all patients and the following MMP-9 genetic polymorphisms were analyzed: C(-1562)T (rs3918242), -90 (CA)(14-24) (rs2234681) and Q279R (rs17576). Haplo.stats analysis was used to assess whether MMP-9 haplotypes are associated with hypertension. Linear regression analysis was performed to assess whether MMP-9 haplotypes affect LV mass index (LVMI) and other echocardiography parameters.
MMP-9 -90 (CA)(14-24) "HH" genotype (H allele defined by number of CA repeats ≥21) was associated with hypertension (P=0.0085; OR=2.321, 95% confidence interval=1.250 to 4.309). While one MMP-9 haplotype ("C, H, Q") protects against LVMI and end-diastolic diameter increases due to remodeling (P=0.0490 and P=0.0367), another MMP-9 haplotype apparently has detrimental effects over both parameters in hypertensive patients ("T, H, Q", P=0.0015 and P=0.0057, respectively).
Genetic polymorphisms in MMP-9 gene may modify the susceptibility of hypertensive patients to LV remodeling. Further studies are necessary to examine whether these polymorphisms affect clinical events in hypertensive patients.
基质金属蛋白酶(MMPs)参与心脏重构,其基因表现出遗传多态性,具有功能意义。我们研究了 MMP-9 基因多态性与高血压以及高血压患者左心室重构的关系。
我们研究了 173 例高血压患者和 137 例年龄、种族和性别匹配的健康对照者。所有患者均行心脏超声心动图检查,并分析 MMP-9 基因的以下遗传多态性:C(-1562)T(rs3918242)、-90(CA)(14-24)(rs2234681)和 Q279R(rs17576)。采用 haplo.stats 分析评估 MMP-9 单倍型与高血压的关系。采用线性回归分析评估 MMP-9 单倍型对左心室质量指数(LVMI)和其他超声心动图参数的影响。
MMP-9-90(CA)(14-24)“HH”基因型(H 等位基因定义为 CA 重复次数≥21)与高血压相关(P=0.0085;OR=2.321,95%可信区间=1.250-4.309)。虽然一种 MMP-9 单倍型(“C、H、Q”)可预防 LVMI 和因重构引起的舒张末期直径增加(P=0.0490 和 P=0.0367),但另一种 MMP-9 单倍型在高血压患者中对这两个参数似乎均有不利影响(“T、H、Q”,P=0.0015 和 P=0.0057)。
MMP-9 基因的遗传多态性可能改变高血压患者发生 LV 重构的易感性。需要进一步研究这些多态性是否影响高血压患者的临床事件。