Pharmacogenetic associations of MMP9 and MMP12 variants with cardiovascular disease in patients with hypertension.
Pharmacogenetic associations of MMP9 and MMP12 variants with cardiovascular disease in patients with hypertension.
复制标题
DOI：
10.1371/journal.pone.0023609
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Arnett DK
中科院分区：
文献类型：
--
作者：
Tanner RM;Lynch AI;Brophy VH;Eckfeldt JH;Davis BR;Ford CE;Boerwinkle E;Arnett DK
MMP-9 和-12 在组织重塑中发挥作用，并可能在心血管疾病 (CVD) 中发挥作用。我们评估了四种 MMP 多态性和三种抗高血压药物与心血管结局的关联。来自双盲、随机临床试验的高血压患者 (n = 42,418) 被随机接受氯噻酮、氨氯地平、赖诺普利或多沙唑嗪治疗（平均随访时间为 4.9 年）。主要结局是冠心病（CHD）。次要结局包括合并 CHD、所有 CVD 结局合并、中风、心力衰竭 (HF) 和死亡率。测试了基因型与治疗的相互作用。共有 38,698 名参与者至少对此处包含的一种多态性进行了基因分型。对于 MMP9 R668Q (rs2274756)，发现 AA 受试者在接受氯噻酮治疗时，大多数结果的风险比 (HR) 低于氨氯地平 (例如，CCHD：GG = 1.00，GA = 1.01，AA = 0.64；P = 0.038)。对于 MMP9 R279Q (rs17576)，在组合 CHD 和复合 CVD 结果中观察到适度的药物遗传学发现。对于 MMP12 N122S (rs652438)，在携带至少一个 G 等位基因并接受氯噻酮治疗的受试者中，与赖诺普利相比，观察到 CHD 的 HR 较低 (CHD：AA = 1.07，AG = 0.80，GG = 0.49；P = 0.005)。在赖诺普利-氨氯地平比较中，MMP12 N122S 基因座上至少有一个 G 等位基因的参与者观察到较高的 HR（CHD：AA = 0.94，AG = 1.19，GG = 1.93；P = 0.041）。对于 MMP12 -82A>G (rs2276109)，虽然在氯噻酮-氨氯地平与 HF 的比较中观察到 AA 纯合子的 HR 较低，但未发现主要结局的药物遗传学效应 (P = 0.015)。我们观察了抗高血压药物与 MMP9 和 MMP12 之间对于 CHD 和复合 CVD 的相互作用。数据表明这些基因可能为治疗决策提供有用的临床信息。
MMP-9 and -12 function in tissue remodeling and may play roles in cardiovascular disease (CVD). We assessed associations of four MMP polymorphisms and three antihypertensive drugs with cardiovascular outcomes. Hypertensives (n = 42,418) from a double-blind, randomized, clinical trial were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatment (mean follow up, 4.9 years). The primary outcome was coronary heart disease (CHD). Secondary outcomes included combined CHD, all CVD outcomes combined, stroke, heart failure (HF), and mortality. Genotype-treatment interactions were tested. There were 38,698 participants genotyped for at least one of the polymorphisms included here. For MMP9 R668Q (rs2274756), lower hazard ratios (HRs) were found for AA subjects for most outcomes when treated with chlorthalidone versus amlodipine (eg., CCHD: GG = 1.00, GA = 1.01, AA = 0.64; P = 0.038). For MMP9 R279Q (rs17576), modest pharmacogenetic findings were observed for combined CHD and the composite CVD outcome. For MMP12 N122S (rs652438), lower HRs were observed for CHD in subjects carrying at least one G allele and being treated with chlorthalidone versus lisinopril (CHD: AA = 1.07, AG = 0.80, GG = 0.49; P = 0.005). In the lisinopril-amlodipine comparison, higher HRs were observed for participants having at least one G allele at the MMP12 N122S locus (CHD: AA = 0.94, AG = 1.19, GG = 1.93; P = 0.041). For MMP12 −82A>G (rs2276109), no pharmacogenetic effect was found for the primary outcome, although lower HRs were observed for AA homozygotes in the chlorthalidone-amlodipine comparison for HF (P = 0.015). We observed interactions between antihypertensive drugs and MMP9 and MMP12 for CHD and composite CVD. The data suggest that these genes may provide useful clinical information with respect to treatment decisions.
登录
查看更多内容
DOI：
10.1073/pnas.0506201102
发表时间：
2005-10-25
影响因子：
11.1
作者：
Johnson, JL;George, SJ;Jackson, CL
通讯作者：
Jackson, CL
影响因子：
3.5
作者：
Joos, L;He, JQ;Sandford, AJ
通讯作者：
Sandford, AJ
影响因子：
2.8
作者：
Jguirim-Souissi, Imen;Jelassi, Awatef;Slimane, Mohamed Naceur
通讯作者：
Slimane, Mohamed Naceur
影响因子：
3.2
作者：
Davis, BR;Cutler, JA;Hawkins, CM
通讯作者：
Hawkins, CM
影响因子：
4.8
作者：
Hlatky, Mark A.;Ashley, Euan;Go, Alan S.
通讯作者：
Go, Alan S.