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MYLK 基因变异与儿童和成人社区获得性肺炎肺损伤的关系。

Genetic variation in MYLK and lung injury in children and adults with community-acquired pneumonia.

机构信息

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.

出版信息

Pediatr Crit Care Med. 2010 Nov;11(6):731-6. doi: 10.1097/PCC.0b013e3181ce7497.

Abstract

OBJECTIVE

To investigate whether selected single nucleotide polymorphisms in the myosin light chain kinase gene are associated with more severe lung injury in children and adults with community-acquired pneumonia. Previous studies have demonstrated an association between single nucleotide polymorphisms in the myosin light chain kinase gene and increased severity of acute lung injury in adults.

DESIGN

Prospective, case-control genetic association study.

SETTING

Three tertiary children's hospitals and one adult healthcare system.

PATIENTS

A total of 800 pediatric patients and 393 adult patients.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

Genetic variation in the myosin light chain kinase gene was examined. The pediatric cohort was predominantly composed of African American (n = 443) and Caucasian (n = 253) children. A total of 393 patients made up the adult cohort. Within the pediatric cohort, single nucleotide polymorphisms rs16834493, rs820463, and rs9840993 were genotyped in the African American patients, whereas single nucleotide polymorphisms rs960224, rs33264, rs11718105, and rs9289225 were genotyped in the Caucasian patients. One single nucleotide polymorphism (rs820336) was genotyped in both groups. Genotyping in the adult cohort included rs820336, rs860224, rs33264, and rs11718105. Genotyping was performed using the Taqman Assay. Data were analyzed separately for African Americans and Caucasians and for children and adults. No associations were observed between the myosin light chain kinase gene single nucleotide polymorphisms genotyped in children with community-acquired pneumonia and increased severity of lung injury. Similarly, no associations were observed between myosin light chain kinase gene single nucleotide polymorphisms genotyped in adults with community-acquired pneumonia and increased severity of lung injury.

CONCLUSIONS

No association between the selected single nucleotide polymorphisms in the myosin light chain kinase gene and either the need for positive-pressure ventilation or the development of acute lung injury/acute respiratory distress syndrome was observed in children with community-acquired pneumonia. This suggests that variation in this gene may play less of a role in lung injury in children or adults with community-acquired pneumonia than in adults with sepsis or trauma.

摘要

目的

研究肌球蛋白轻链激酶基因中的某些单核苷酸多态性是否与社区获得性肺炎患儿和成人的更严重肺损伤有关。先前的研究表明,肌球蛋白轻链激酶基因中的单核苷酸多态性与成人急性肺损伤的严重程度增加有关。

设计

前瞻性病例对照遗传关联研究。

地点

三家三级儿童医院和一家成人保健系统。

患者

共 800 名儿科患者和 393 名成年患者。

干预措施

无。

测量和主要结果

检查了肌球蛋白轻链激酶基因的遗传变异。儿科队列主要由非裔美国人(n=443)和白人(n=253)儿童组成。共有 393 名患者组成了成人队列。在儿科队列中,对非裔美国人患者进行了单核苷酸多态性 rs16834493、rs820463 和 rs9840993 的基因分型,而对白人患者进行了单核苷酸多态性 rs960224、rs33264、rs11718105 和 rs9289225 的基因分型。一个单核苷酸多态性(rs820336)在两组中都进行了基因分型。成人队列的基因分型包括 rs820336、rs860224、rs33264 和 rs11718105。基因分型使用 Taqman 分析进行。数据分别在非裔美国人和白人和儿童及成人中进行分析。在患有社区获得性肺炎的儿童中,与肌球蛋白轻链激酶基因单核苷酸多态性相关的基因分型与肺损伤严重程度的增加之间没有关联。同样,在患有社区获得性肺炎的成人中,与肌球蛋白轻链激酶基因单核苷酸多态性相关的基因分型与肺损伤严重程度的增加之间也没有关联。

结论

在患有社区获得性肺炎的儿童中,与肌球蛋白轻链激酶基因中的选定单核苷酸多态性与需要正压通气或发生急性肺损伤/急性呼吸窘迫综合征之间没有关联。这表明,与败血症或创伤患者相比,该基因的变异在儿童或成人社区获得性肺炎患者的肺损伤中可能作用较小。

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