Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: a prospective, observational, genetic study.
Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: a prospective, observational, genetic study.
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DOI：
10.1186/cc10030
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Rodríguez-Gallego C
中科院分区：
文献类型：
--
作者：
García-Laorden MI;Rodríguez de Castro F;Solé-Violán J;Rajas O;Blanquer J;Borderías L;Aspa J;Briones ML;Saavedra P;Marcos-Ramos JA;González-Quevedo N;Sologuren I;Herrera-Ramos E;Ferrer JM;Rello J;Rodríguez-Gallego C
肺表面活性蛋白A和D的遗传变异性可能影响微生物的清除和炎症反应的程度。这些凝集素（SFTPA 1、SFTPA 2和SFTPD）的基因位于10 q21 -24的簇中。本研究的目的是评估这些基因之间是否存在连锁不平衡（LD），以及这些基因的变异性与社区获得性肺炎（CAP）的易感性和结局的相关性。我们还研究了遗传变异对SP-D血清水平的影响。分析了SFTPA 1、SFTPA 2和SFTPD的7个非同义多态性。在病例对照研究中，对682例CAP患者和769例对照进行了易感性研究。在一项前瞻性研究中评价了严重程度和结局。单倍型推断和LD的特点。在健康对照中测量SP-D血清水平。SFTPD aa 11-C等位基因以剂量依赖性方式与较低的SP-D血清水平显著相关。我们观察到在所研究的基因中存在LD。单倍型SFTPA 1 6A 2（P = 0.0009，OR = 0.78），SFTPA2 1A0（P = 0.002，OR = 0.79），SFTPA1-SFTPA2 6A2-1A0（P = 0.0005，OR = 0.77）和SFTPD-SFTPA1-SFTPA2 C-6A2-1A0（P = 0.00001，OR = 0.62）在患者中的代表性不足，而单倍型SFTPA 2 1A 10（P = 0.00007，OR = 6.58）和SFTPA 1-SFTPA 2 6A 3 -1A（P = 0.0007，OR = 3.92）的代表性过高。在肺炎球菌引起的CAP中观察到类似的结果，尽管在Bonferroni校正后没有观察到显著差异。1A 10和6A-1A分别与较高的28天和90天死亡率、多器官功能障碍综合征（MODS）和急性呼吸窘迫综合征（ARDS）相关。SFTPDaa 11-C等位基因与MODS和ARDS的发生有关。我们的研究表明，SFTPA 1，SFTPA 2和SFTPD的错义单核苷酸多态性和单倍型与CAP的易感性相关，并且几种单倍型也影响CAP的严重程度和结果。
Genetic variability of the pulmonary surfactant proteins A and D may affect clearance of microorganisms and the extent of the inflammatory response. The genes of these collectins (SFTPA1, SFTPA2 and SFTPD) are located in a cluster at 10q21-24. The objective of this study was to evaluate the existence of linkage disequilibrium (LD) among these genes, and the association of variability at these genes with susceptibility and outcome of community-acquired pneumonia (CAP). We also studied the effect of genetic variability on SP-D serum levels. Seven non-synonymous polymorphisms of SFTPA1, SFTPA2 and SFTPD were analyzed. For susceptibility, 682 CAP patients and 769 controls were studied in a case-control study. Severity and outcome were evaluated in a prospective study. Haplotypes were inferred and LD was characterized. SP-D serum levels were measured in healthy controls. The SFTPD aa11-C allele was significantly associated with lower SP-D serum levels, in a dose-dependent manner. We observed the existence of LD among the studied genes. Haplotypes SFTPA1 6A2 (P = 0.0009, odds ration (OR) = 0.78), SFTPA2 1A0 (P = 0.002, OR = 0.79), SFTPA1-SFTPA2 6A2-1A0 (P = 0.0005, OR = 0.77), and SFTPD-SFTPA1-SFTPA2 C-6A2-1A0 (P = 0.00001, OR = 0.62) were underrepresented in patients, whereas haplotypes SFTPA2 1A10 (P = 0.00007, OR = 6.58) and SFTPA1-SFTPA2 6A3-1A (P = 0.0007, OR = 3.92) were overrepresented. Similar results were observed in CAP due to pneumococcus, though no significant differences were now observed after Bonferroni corrections. 1A10 and 6A-1A were associated with higher 28-day and 90-day mortality, and with multi-organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) respectively. SFTPD aa11-C allele was associated with development of MODS and ARDS. Our study indicates that missense single nucleotide polymorphisms and haplotypes of SFTPA1, SFTPA2 and SFTPD are associated with susceptibility to CAP, and that several haplotypes also influence severity and outcome of CAP.
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影响因子：
5.1
作者：
El Saleeby, Chadi M.;Li, Rongling;DeVincenzo, John P.
通讯作者：
DeVincenzo, John P.
DOI：
10.1165/ajrcmb.15.4.8879183
发表时间：
1996-10-01
影响因子：
6.4
作者：
Floros, J;DiAngelo, S;Deiter, G
通讯作者：
Deiter, G
DOI：
10.1152/ajplung.1994.267.5.l578
发表时间：
1994-11-01
影响因子：
4.9
作者：
GEERTSMA, MF;NIBBERING, PH;VANFURTH, R
通讯作者：
VANFURTH, R
DOI：
10.1152/ajplung.00118.2002
发表时间：
2002-11-01
影响因子：
4.9
作者：
Hawgood, S;Ochs, M;Poulain, FR
通讯作者：
Poulain, FR
DOI：
10.1164/ajrccm.160.6.9901117
发表时间：
1999-12-01
影响因子：
24.7
作者：
Greene, KE;Wright, JR;Martin, TR
通讯作者：
Martin, TR