A functional polymorphism in renalase (Glu37Asp) is associated with cardiac hypertrophy, dysfunction, and ischemia: data from the heart and soul study.
A functional polymorphism in renalase (Glu37Asp) is associated with cardiac hypertrophy, dysfunction, and ischemia: data from the heart and soul study.
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DOI：
10.1371/journal.pone.0013496
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发表时间：
2010-10-20
期刊：
影响因子：
3.7
通讯作者：
Whooley MA
中科院分区：
文献类型：
--
作者：
Farzaneh-Far R;Desir GV;Na B;Schiller NB;Whooley MA
肾酶是一种可溶性酶，代谢循环中的儿茶酚胺。一种常见的错义多态性在黄素腺嘌呤二核苷酸结合域的人肾酶（Glu 37 Asp）最近已被描述。这种多态性与心脏结构、功能和缺血的关联以前未见报道。我们对590名高加索人的rs 2296545单核苷酸多态性（Glu 37 Asp）进行了基因分型，并进行了静息和负荷超声心动图检查。采用Logistic回归分析Glu 37 Asp多态性（C等位基因）与心肌肥厚（左室质量>100 g/m2）、收缩功能不全（LVEF<50%）、舒张功能不全、平板运动能力差（METS<5）和诱发性心肌缺血的关系。与406名GG或CG基因型受试者相比，184名CC基因型受试者发生左心室肥大（OR = 1.43; 95%CI 0.99-2.06）、收缩功能障碍（OR = 1.72; 95%CI 1.01-2.94）、舒张功能障碍（OR = 1.75; 95%CI 1.05-2.93）、运动能力差（OR = 1.61; 95%CI 1.05-2.47）和可诱导缺血（OR = 1.49，95%CI 0.99-2.24）的几率增加。 Glu 37 Asp（CC基因型）导致了24倍的亲和力下降，为NADH和2.3倍的最大肾酶活性降低。肾酶（Glu 37 Asp）的功能性错义多态性与稳定型冠状动脉疾病患者的心肌肥厚、心室功能障碍、运动能力差和可诱导缺血相关应考虑进一步研究这种多态性的治疗意义。
Renalase is a soluble enzyme that metabolizes circulating catecholamines. A common missense polymorphism in the flavin-adenine dinucleotide-binding domain of human renalase (Glu37Asp) has recently been described. The association of this polymorphism with cardiac structure, function, and ischemia has not previously been reported. We genotyped the rs2296545 single-nucleotide polymorphism (Glu37Asp) in 590 Caucasian individuals and performed resting and stress echocardiography. Logistic regression was used to examine the associations of the Glu37Asp polymorphism (C allele) with cardiac hypertrophy (LV mass>100 g/m2), systolic dysfunction (LVEF<50%), diastolic dysfunction, poor treadmill exercise capacity (METS<5) and inducible ischemia. Compared with the 406 participants who had GG or CG genotypes, the 184 participants with the CC genotype had increased odds of left ventricular hypertrophy (OR = 1.43; 95% CI 0.99–2.06), systolic dysfunction (OR = 1.72; 95% CI 1.01–2.94), diastolic dysfunction (OR = 1.75; 95% CI 1.05–2.93), poor exercise capacity (OR = 1.61; 95% CI 1.05–2.47), and inducible ischemia (OR = 1.49, 95% CI 0.99–2.24). The Glu37Asp (CC genotype) caused a 24-fold decrease in affinity for NADH and a 2.3-fold reduction in maximal renalase enzymatic activity. A functional missense polymorphism in renalase (Glu37Asp) is associated with cardiac hypertrophy, ventricular dysfunction, poor exercise capacity, and inducible ischemia in persons with stable coronary artery disease. Further studies investigating the therapeutic implications of this polymorphism should be considered.
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影响因子：
2.8
作者：
Ren, Xiushui;Ristow, Bryan;Whooley, Mary A.
通讯作者：
Whooley, Mary A.
影响因子：
120.7
作者：
Culleton, Bruce F.;Walsh, Michael;Manns, Braden J.
通讯作者：
Manns, Braden J.
影响因子：
24
作者：
Oh, JK;Hatle, L;Little, WC
通讯作者：
Little, WC
DOI：
10.1016/s1387-2656(05)11004-7
发表时间：
2005-01-01
期刊：
BIOTECHNOLOGY ANNUAL REVIEW, VOL 11
影响因子：
--
作者：
Berridge, MV;Herst, PM;Tan, AS
通讯作者：
Tan, AS
影响因子：
19.6
作者：
Neumann, J;Ligtenberg, G;Blankestijn, PJ
通讯作者：
Blankestijn, PJ