Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy.
Adipocyte-derived leucine aminopeptidase genotype and response to antihypertensive therapy.
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DOI：
10.1186/1471-2261-3-11
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发表时间：
2003-09-18
影响因子：
2.1
通讯作者：
Melhus H
中科院分区：
文献类型：
--
作者：
Hallberg P;Lind L;Michaëlsson K;Kurland L;Kahan T;Malmqvist K;Ohman KP;Nyström F;Liljedahl U;Syvänen AC;Melhus H
脂肪细胞来源的亮氨酸氨肽酶（阿拉普）是最近鉴定的锌金属肽酶M1家族的成员，并且被认为通过使血管紧张素II失活和/或产生缓激肽而在血压控制中起作用。这种酶似乎在心脏中特别丰富。最近，阿拉普基因的Arg 528编码等位基因被证明与原发性高血压相关。我们评估了这种多态性对90例原发性高血压和超声心动图诊断的左心室肥厚患者左心室质量指数变化的影响，这些患者在一项双盲研究中随机接受血管紧张素II I型受体拮抗剂厄贝沙坦或β 1肾上腺素受体阻滞剂阿替洛尔治疗48周。使用微测序进行基因分型。调整潜在协变量后（基线时血压和左心室质量指数、血压变化、年龄、性别、剂量和是否加用降压药），厄贝沙坦组Arg/Arg和Lys/Arg基因型之间有显著差异; Arg/Arg基因型患者的左心室质量指数平均下降幅度比Lys/Arg基因型患者高近两倍。Arg基因型（-30.1 g/m2 [3.6] vs-16.7 [4.5]，p = 0.03）。阿拉普基因型似乎决定了原发性高血压和左心室肥厚患者在血管紧张素II I型受体拮抗剂厄贝沙坦降压治疗期间左心室肥厚的消退程度。这是第一份关于阿拉普/氨肽酶在左心室质量调节中作用的报告，并提出了抗高血压药物的新潜在靶点。
Adipocyte-derived leucine aminopeptidase (ALAP) is a recently identified member of the M1 family of zinc-metallopeptidases and is thought to play a role in blood pressure control through inactivation of angiotensin II and/or generation of bradykinin. The enzyme seems to be particularly abundant in the heart. Recently, the Arg528-encoding allele of the ALAP gene was shown to be associated with essential hypertension. We evaluated the influence of this polymorphism on the change in left ventricular mass index in 90 patients with essential hypertension and echocardiographically diagnosed left ventricular hypertrophy, randomised in a double-blind study to receive treatment with either the angiotensin II type I receptor antagonist irbesartan or the beta1-adrenoceptor blocker atenolol for 48 weeks. Genyotyping was performed using minisequencing. After adjustment for potential covariates (blood pressure and left ventricular mass index at baseline, blood pressure change, age, sex, dose and added antihypertensive treatment), there was a marked difference between the Arg/Arg and Lys/Arg genotypes in patients treated with irbesartan; those with the Arg/Arg genotype responded on average with an almost two-fold greater regression of left ventricular mass index than patients with the Lys/Arg genotype (-30.1 g/m2 [3.6] vs -16.7 [4.5], p = 0.03). The ALAP genotype seems to determine the degree of regression of left ventricular hypertrophy during antihypertensive treatment with the angiotensin II type I receptor antagonist irbesartan in patients with essential hypertension and left ventricular hypertrophy. This is the first report of a role for ALAP/aminopeptidases in left ventricular mass regulation, and suggests a new potential target for antihypertensive drugs.
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影响因子：
2.7
作者：
Hattori, A;Matsumoto, H;Tsujimoto, M
通讯作者：
Tsujimoto, M
影响因子：
8.3
作者：
Healy, DP;Song, LJ
通讯作者：
Song, LJ
影响因子：
2.7
作者：
Hattori, A;Kitatani, K;Tsujimoto, M
通讯作者：
Tsujimoto, M
影响因子：
3.9
作者：
Yamamoto, N;Nakayama, J;Arinami, T
通讯作者：
Arinami, T
影响因子：
39.2
作者：
KOREN, MJ;DEVEREUX, RB;LARAGH, JH
通讯作者：
LARAGH, JH