Atenolol induced HDL-C change in the pharmacogenomic evaluation of antihypertensive responses (PEAR) study.
Atenolol induced HDL-C change in the pharmacogenomic evaluation of antihypertensive responses (PEAR) study.
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DOI：
10.1371/journal.pone.0076984
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Johnson JA
中科院分区：
文献类型：
--
作者：
McDonough CW;Gillis NK;Alsultan A;Chang SW;Kawaguchi-Suzuki M;Lang JE;Shahin MH;Buford TW;El Rouby NM;Sá AC;Langaee TY;Gums JG;Chapman AB;Cooper-DeHoff RM;Turner ST;Gong Y;Johnson JA
我们试图在轻度至中度高血压患者中确定阿替洛尔对HDL-C反应的新药物基因组学标志物。我们在Illumina HumanCVD Beadchip上对来自抗高血压反应药物基因组学评价（PEAR）研究的768名高血压参与者进行了基因分型。在PEAR期间，参与者被随机分配接受阿替洛尔或氢氯噻嗪。在基线和治疗后评估血压和胆固醇水平。本研究的重点是接受阿替洛尔单药治疗的受试者。使用线性回归法在232名白人和152名非裔美国人中评估了阿替洛尔诱导的HDL-C变化的相关性。没有SNP达到Bonferroni校正的P值。然而，我们确定了13个在白人和非洲裔美国人之间具有一致关联的地区。这些区域中最有趣的是7个先前与HDL-C，其他代谢特征或脂质途径中的功能性影响相关的区域：GALNT 2，FTO，ABCB 1，LRP 5，STARD 3 NL，ESR 1和LIPC。例如，白人中GALNT 2中的rs 2144300（P= 2.29 × 10 -4，β=-1.85 mg/dL）和非裔美国人中FTO中的rs 12595985（P= 2.90 × 10 -4，β=4.52 mg/dL），在其他种族组中两者均具有一致的区域关联（P<0.05）。此外，在白人中，基线GALNT 2表达因rs 2144300基因型而异（P=0.0279）。总之，我们确定了与阿替洛尔诱导的HDL-C变化相关的多个基因区域，这些基因区域在不同种族群体中是一致的，其中几个具有功能意义或与HDL-C先前相关。
We sought to identify novel pharmacogenomic markers for HDL-C response to atenolol in participants with mild to moderate hypertension. We genotyped 768 hypertensive participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study on the Illumina HumanCVD Beadchip. During PEAR, participants were randomized to receive atenolol or hydrochlorothiazide. Blood pressure and cholesterol levels were evaluated at baseline and after treatment. This study focused on participants treated with atenolol monotherapy. Association with atenolol induced HDL-C change was evaluated in 232 whites and 152 African Americans using linear regression. No SNPs achieved a Bonferroni corrected P-value. However, we identified 13 regions with consistent association across whites and African Americans. The most interesting of these regions were seven with prior associations with HDL-C, other metabolic traits, or functional implications in the lipid pathway: GALNT2, FTO, ABCB1, LRP5, STARD3NL, ESR1, and LIPC. Examples are rs2144300 in GALNT2 in whites (P=2.29x10-4, β=-1.85 mg/dL) and rs12595985 in FTO in African Americans (P=2.90x10-4, β=4.52 mg/dL), both with consistent regional association (P<0.05) in the other race group. Additionally, baseline GALNT2 expression differed by rs2144300 genotype in whites (P=0.0279). In conclusion, we identified multiple gene regions associated with atenolol induced HDL-C change that were consistent across race groups, several with functional implications or prior associations with HDL-C.
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影响因子：
4.8
作者：
Johnson, Julie A.;Boerwinkle, Eric;Zineh, Issain;Chapman, Arlene B.;Bailey, Kent;Cooper-DeHoff, Rhonda M.;Gums, John;Curry, R. Whit;Gong, Yan;Beitelshees, Amber L.;Schwartz, Gary;Turner, Stephen T.
通讯作者：
Turner, Stephen T.
影响因子：
158.5
作者：
Barter, Philip;Gotto, Antonio M.;Fruchart, Jean-Charles
通讯作者：
Fruchart, Jean-Charles
影响因子：
64.5
作者：
KINGSLEY, DM;KOZARSKY, KF;KRIEGER, M
通讯作者：
KRIEGER, M
DOI：
10.1093/bioinformatics/btn653
发表时间：
2009-03-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Chelala C;Khan A;Lemoine NR
通讯作者：
Lemoine NR
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.