Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome.
Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome.
复制标题
ADRB1 和 CYP2C9 的变异：与马凡综合征中阿替洛尔和氯沙坦的反应相关。
DOI：
10.1016/j.jpeds.2020.03.064
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Meester,Jose
中科院分区：
文献类型：
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作者：
VanDriest,SaraL;Sleeper,LynnA;Gelb,BruceD;Morris,ShaineA;Dietz,HarryC;Forbus,GeoffreyA;Goldmuntz,Elizabeth;Hoskoppal,Arvind;James,Jeanne;Lee,TeresaM;Levine,JamiC;Li,JenniferS;Loeys,BartL;Markham,LarryW;Meester,Jose
目的通过分析一项大型随机试验的数据，测试ADRB 1和CYP 2C 9基因变异是否可以识别对马凡氏综合症治疗有不同反应的个体亚组。研究设计在先前的一项随机试验中，阿替洛尔与氯沙坦的比较中，有250名患有马凡氏综合症的白色、非西班牙裔参与者，对ADRB 1的常见变异rs 1801252和rs 1801253以及CYP 2C 9的常见变异rs 1799853和rs 1057910进行分析。主要结果是基线调整的年变化率的最大主动脉根部直径z评分超过3年，评估使用混合效应models.ResultsAmong 122阿替洛尔分配的参与者，70与rs 1801253 CC基因型有更大的改善率主动脉根部z评分相比，52与CG或GG基因型的参与者（时间×基因型相互作用P = 0.005，平均年z评分变化± SE-0.20 ± 0.03 vs-0.09 ± 0.03）。在两个治疗组中CC基因型的参与者中，阿替洛尔组的改善率高于氯沙坦组的71/121（相互作用P = 0.002; −0.20 ± 0.02 vs −0.07 ± 0.02;P<0.001）。阿替洛尔反应rs 1801252基因型或氯沙坦反应CYP 2C 9 metabolizer status.ConclusionsIn this explorative study，ADRB 1-rs 1801253与阿替洛尔反应马凡氏综合征的儿童和年轻人相关。如果这些发现在未来的研究中得到证实，ADRB 1基因分型有可能通过识别那些对阿替洛尔的治疗反应可能比氯沙坦更大的患者来指导治疗。
ObjectiveTo test whether variants inADRB1andCYP2C9genes identify subgroups of individuals with differential response to treatment for Marfan syndrome through analysis of data from a large, randomized trial.Study designIn a subset of 250 white, non-Hispanic participants with Marfan syndrome in a prior randomized trial of atenolol vs losartan, the common variants rs1801252 and rs1801253 inADRB1and rs1799853 and rs1057910 inCYP2C9were analyzed. The primary outcome was baseline-adjusted annual rate of change in the maximum aortic root diameter z-score over 3 years, assessed using mixed effects models.ResultsAmong 122 atenolol-assigned participants, the 70 with rs1801253 CC genotype had greater rate of improvement in aortic root z-score compared with 52 participants with CG or GG genotypes (Time × Genotype interactionP= .005, mean annual z-score change ± SE –0.20 ± 0.03 vs −0.09 ± 0.03). Among participants with the CC genotype in both treatment arms, those assigned to atenolol had greater rate of improvement compared with the 71 of the 121 assigned to losartan (interactionP= .002; −0.20 ± 0.02 vs −0.07 ± 0.02;P< .001). There were no differences in atenolol response by rs1801252 genotype or in losartan response by CYP2C9 metabolizer status.ConclusionsIn this exploratory study,ADRB1-rs1801253 was associated with atenolol response in children and young adults with Marfan syndrome. If these findings are confirmed in future studies,ADRB1genotyping has the potential to guide therapy by identifying those who are likely to have greater therapeutic response to atenolol than losartan.