Heme oxygenase-1 microsatellite polymorphism and haplotypes are associated with the development of acute respiratory distress syndrome.
Heme oxygenase-1 microsatellite polymorphism and haplotypes are associated with the development of acute respiratory distress syndrome.
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DOI：
10.1007/s00134-009-1504-6
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发表时间：
2009-08
影响因子：
38.9
通讯作者：
Christiani, David C.
中科院分区：
文献类型：
--
作者：
Sheu, Chau-Chyun;Zhai, Rihong;Wang, Zhaoxi;Gong, Michelle N.;Tejera, Paula;Chen, Feng;Su, Li;Thompson, B. Taylor;Christiani, David C.
关键词：
血红素氧合酶-1（HO-1）对急性肺损伤具有细胞保护作用。HO-1基因（HMOX 1）启动子中的多态性（GT）n重复序列调控HMOX 1的表达。我们研究了HMOX 1基因多态性与ARDS风险和血浆HO-1水平的关系。非匹配、巢式病例对照研究。学术医疗中心。前瞻性入选ICU入院时有ARDS危险因素的连续性患者。病例为437例发生ARDS的白种人，对照组为1014例未发生ARDS的白种人。我们对1451例患者进行了（GT）n多态性和3个标签单核苷酸多态性（tSNPs）基因分型，并测定了106例ARDS患者的血浆HO-1水平。我们将（GT）n重复序列分为S等位基因（< 24个重复）、M等位基因（24-30个重复）和L等位基因（≥ 31个重复）。我们发现较长的（GT）n重复序列与降低的ARDS风险相关（等位基因和基因型的P趋势= 0.004），但没有个体tSNP与ARDS风险相关。HMOX 1单倍型与ARDS风险显著相关（总体检验，P = 0.016），单倍型S-TAG与ARDS风险增加相关（OR，1.75; 95%CI，1.15-2.68; P = 0.010）。中间表型分析显示，更长的（GT）n重复与更高的血浆HO-1水平相关（P趋势= 0.019等位基因和0.027基因型）。HMOX 1启动子中较长的（GT）n重复序列与较高的血浆HO-1水平和降低的ARDS风险相关。常见单倍型S-TAG与ARDS风险增加相关。我们的研究结果表明，HMOX 1变异可能通过启动子微卫星多态性调节ARDS风险。
Heme oxygenase-1 (HO-1) acts in cytoprotection against acute lung injury. The polymorphic (GT)n repeat in the HO-1 gene (HMOX1) promoter regulates HMOX1 expression. We investigated the associations of HMOX1 polymorphisms with ARDS risk and plasma HO-1 levels. Unmatched, nested case-control study. Academic medical center. Consecutive patients with ARDS risk factors upon ICU admission were prospectively enrolled. Cases were 437 Caucasians who developed ARDS and controls were 1014 Caucasians who did not. We genotyped the (GT)n polymorphism and three tagging single nucleotide polymorphisms (tSNPs) in 1451 patients, and measured the plasma HO-1 levels in 106 ARDS patients. We clustered the (GT)n repeats into: S-allele (< 24 repeats), M-allele (24–30 repeats) and L-allele (≥ 31 repeats). We found that longer (GT)n repeats were associated with reduced ARDS risk (Ptrend = 0.004 for both alleles and genotypes), but no individual tSNP was associated with ARDS risk. HMOX1 haplotypes were significantly associated with ARDS risk (global test, P = 0.016), and the haplotype S-TAG was associated with increased ARDS risk (OR, 1.75; 95% CI, 1.15–2.68; P = 0.010). Intermediate-phenotype analysis showed longer (GT)n repeats were associated with higher plasma HO-1 levels (Ptrend = 0.019 for alleles and 0.027 for genotypes). Longer (GT)n repeats in the HMOX1 promoter are associated with higher plasma HO-1 levels and reduced ARDS risk. The common haplotype S-TAG is associated with increased ARDS risk. Our results suggest that HMOX1 variation may modulate ARDS risk through the promoter microsatellite polymorphism.
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影响因子：
8.8
作者：
Gong, MN;Thompson, BT;Christiani, DC
通讯作者：
Christiani, DC
影响因子：
8.8
作者：
Buis, C. I.;van der Steege, G.;Porte, R. J.
通讯作者：
Porte, R. J.
影响因子：
1.6
作者：
Fredenburgh, LE;Baron, RM;Perrella, MA
通讯作者：
Perrella, MA
DOI：
10.1164/rccm.200706-863oc
发表时间：
2008-02-15
影响因子：
24.7
作者：
Islam, Talat;McConnell, Rob;Gilliland, Frank D.
通讯作者：
Gilliland, Frank D.
影响因子：
8.8
作者：
Courtney, A. E.;McNamee, P. T.;Maxwell, A. P.
通讯作者：
Maxwell, A. P.