Faculty Collaboration Database

Association of polymorphisms in genes of factors involved in regulation of splicing of cystic fibrosis transmembrane conductance regulator mRNA with acute respiratory distress syndrome in children with pneumonia. Crit Care 2016 Sep 05;20(1):281

Date

09/07/2016

Pubmed ID

27596159

Pubmed Central ID

PMC5011993

DOI

10.1186/s13054-016-1454-7

Scopus ID

2-s2.0-84985006621 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

BACKGROUND: Previous work has demonstrated a strong association between lung injury in African American children with pneumonia and a polymorphic (TG)mTn region in cystic fibrosis transmembrane conductance (CFTR) involved in the generation of a nonfunctional CFTR protein lacking exon 9. A number of splicing factors that regulate the inclusion/exclusion of exon 9 have been identified. The objective of this study was to determine whether genetic variants in these splicing factors were associated with acute respiratory distress syndrome (ARDS) in children with pneumonia.

METHODS: This is a prospective cohort genetic association study of lung injury in African American and non-Hispanic Caucasian children with community-acquired pneumonia evaluated in the emergency department or admitted to the hospital. Linkage-disequilibrium-tag single nucleotide polymorphisms (LD-tag SNPs) in genes of the following splicing factors (followed by gene name) involved in exon 9 skipping PTB1 (PTBP1), SRp40 (SFRS1), SR2/ASF (SFRS5), TDP-43 (TARDBP), TIA-1 (TIA1), and U2AF(65) (U2AF2) were genotyped. SNPs in the gene of the splicing factor CELF2 (CELF2) were selected by conservation score. Multivariable analysis was used to examine association between genotypes and ARDS.

RESULTS: The African American cohort (n = 474) had 29 children with ARDS and the non-Hispanic Caucasian cohort (n = 304) had 32 children with ARDS. In the African American group multivariable analysis indicated that three variants in CELF2, rs7068124 (p = 0.004), rs3814634 (p = 0.032) and rs10905928 (p = 0.044), and two in TIA1, rs2592178 (p = 0.005) and rs13402990 (p = 0.018) were independently associated with ARDS. In the non-Hispanic Caucasian group, a single variant in CELF2, rs2277212 (p = 0.014), was associated with increased risk of developing ARDS.

CONCLUSIONS: The data indicate that SNPs in CELF2 may be associated with the risk of developing ARDS in both African American and non-Hispanic Caucasian children with pneumonia and suggest that the potential role of the splicing factor CELF2 in ARDS should be explored further.

Author List

Perez-Marques F, Simpson P, Yan K, Quasney MW, Halligan N, Merchant D, Dahmer MK

Authors

Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
Ke Yan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
CELF Proteins
Child
Child, Preschool
Cohort Studies
Cystic Fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator
Female
Genetic Testing
Genetic Variation
Humans
Infant
Infant, Newborn
Male
Multivariate Analysis
Nerve Tissue Proteins
Pneumonia
Polymorphism, Single Nucleotide
Prospective Studies
RNA, Messenger