Genome-wide association study of survival from sepsis due to
pneumonia: an observational cohort study

J 2015

Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study

RAUTANEN, A.; T.C. MILLS; A.C. GORDON; P. HUTTON; M. STEFFENS et al.

Základní údaje

Originální název

Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study

Autoři

Vydání

LANCET RESPIRATORY MEDICINE, OXFORD, ELSEVIER SCI LTD, 2015, 2213-2600

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 15.328

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/15:00084659

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

MANNOSE-BINDING LECTIN; TYROSINE-KINASE FER; SEPTIC SHOCK; UNITED-STATES; INFECTIOUS-DISEASE; SUSCEPTIBILITY; MORTALITY; POLYMORPHISMS; PHOSPHORYLATION; EPIDEMIOLOGY

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 11. 2015 16:00, Soňa Böhmová

Anotace

V originále

Background Sepsis continues to be a major cause of death, disability; and health-care expenditure worldwide. Despite evidence suggesting that host genetics can influence sepsis outcomes, no specific loci have yet been convincingly replicated. The aim of this study was to identify genetic variants that influence sepsis survival. Methods We did a genome-wide association study in three independent cohorts of white adult patients admitted to intensive care units with sepsis, severe sepsis, or septic shock (as defined by the International Consensus Criteria) due to pneumonia or intra-abdominal infection (cohorts 1-3, n=2534 patients). The primary outcome was 28 day survival. Results for the cohort of patients with sepsis due to pneumonia were combined in a meta-analysis of 1553 patients from all three cohorts, of whom 359 died within 28 days of admission to the intensive-care unit. The most significantly associated single nucleotide polymorphisms (SNPs) were genotyped in a further 538 white patients with sepsis due to pneumonia (cohort 4), of whom 106 died. Findings In the genome-wide meta-analysis of three independent pneumonia cohorts (cohorts 1-3), common variants in the PER gene were strongly associated with survival (p=9.7x10(-8)). Further genotyping of the top associated SNP (rs4957796) in the additional cohort (cohort 4) resulted in a combined p value of 5.6x10(-8) (odds ratio 0.56, 95% CI 0.45-0.69). In a time-to-event analysis, each allele reduced the mortality over 28 days by 44% (hazard ratio for death 0.56, 95% CI 0.45-0.69; likelihood ratio test p=3.4x10(-9), after adjustment for age and stratification by cohort). Mortality was 9.5% in patients carrying the CC genotype, 15.2% in those carrying the TC genotype, and 25.3% in those carrying the TT genotype. No significant genetic associations were identified when patients with sepsis due to pneumonia and intra-abdominal infection were combined. Interpretation We have identified common variants in the PER gene that associate with a reduced risk of death from sepsis due to pneumonia. The PER gene and associated molecular pathways are potential novel targets for therapy or prevention and candidates for the development of biomarkers for risk stratification.

Citovat

RAUTANEN, A.; T.C. MILLS; A.C. GORDON; P. HUTTON; M. STEFFENS; R. NUAMAH; J.D. CHICHE; T. PARKS; S.J. CHAPMAN; E.E. DAVENPORT; K.S. ELLIOTT; J. BION; P. LICHTNER; T. MEITINGER; T.F. WIENKER; M.J. CAULFIELD; C. MEIN; F. BLOOS; I. BOBEK; P. COTOGNI; Vladimír ŠRÁMEK; S. SARAPUU; M. KOBILAY; V.M. RANIERI; J. RELLO; G. SIRGO; Y.G. WEISS; S. RUSSWURM; E.M. SCHNEIDER; K. REINHART; P.A. HOLLOWAY; J.C. KNIGHT; C.S. GARRARD; J. RUSSELL; K.R. WALLEY; F. STUBER; A.V.S. HILL a C.J. HINDS. Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study. LANCET RESPIRATORY MEDICINE. OXFORD: ELSEVIER SCI LTD, 2015, roč. 3, č. 1, s. 53-60. ISSN 2213-2600. Dostupné z: https://doi.org/10.1016/S2213-2600(14)70290-5.

@article{1316980,
   author = {Rautanen, A. and Mills, T.C. and Gordon, A.C. and Hutton, P. and Steffens, M. and Nuamah, R. and Chiche, J.D. and Parks, T. and Chapman, S.J. and Davenport, E.E. and Elliott, K.S. and Bion, J. and Lichtner, P. and Meitinger, T. and Wienker, T.F. and Caulfield, M.J. and Mein, C. and Bloos, F. and Bobek, I. and Cotogni, P. and Šrámek, Vladimír and Sarapuu, S. and Kobilay, M. and Ranieri, V.M. and Rello, J. and Sirgo, G. and Weiss, Y.G. and Russwurm, S. and Schneider, E.M. and Reinhart, K. and Holloway, P.A. and Knight, J.C. and Garrard, C.S. and Russell, J. and Walley, K.R. and Stuber, F. and Hill, A.V.S. and Hinds, C.J.},
   article_location = {OXFORD},
   article_number = {1},
   doi = {https://doi.org/10.1016/S2213-2600(14)70290-5},
   keywords = {MANNOSE-BINDING LECTIN; TYROSINE-KINASE FER; SEPTIC SHOCK; UNITED-STATES; INFECTIOUS-DISEASE; SUSCEPTIBILITY; MORTALITY; POLYMORPHISMS; PHOSPHORYLATION; EPIDEMIOLOGY},
   language = {eng},
   issn = {2213-2600},
   journal = {LANCET RESPIRATORY MEDICINE},
   title = {Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study},
   volume = {3},
   year = {2015}
}

TY  - JOUR
ID  - 1316980
AU  - Rautanen, A. - Mills, T.C. - Gordon, A.C. - Hutton, P. - Steffens, M. - Nuamah, R. - Chiche, J.D. - Parks, T. - Chapman, S.J. - Davenport, E.E. - Elliott, K.S. - Bion, J. - Lichtner, P. - Meitinger, T. - Wienker, T.F. - Caulfield, M.J. - Mein, C. - Bloos, F. - Bobek, I. - Cotogni, P. - Šrámek, Vladimír - Sarapuu, S. - Kobilay, M. - Ranieri, V.M. - Rello, J. - Sirgo, G. - Weiss, Y.G. - Russwurm, S. - Schneider, E.M. - Reinhart, K. - Holloway, P.A. - Knight, J.C. - Garrard, C.S. - Russell, J. - Walley, K.R. - Stuber, F. - Hill, A.V.S. - Hinds, C.J.
PY  - 2015
TI  - Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study
JF  - LANCET RESPIRATORY MEDICINE
VL  - 3
IS  - 1
SP  - 53-60
EP  - 53-60
PB  - ELSEVIER SCI LTD
SN  - 22132600
KW  - MANNOSE-BINDING LECTIN
KW  - TYROSINE-KINASE FER
KW  - SEPTIC SHOCK
KW  - UNITED-STATES
KW  - INFECTIOUS-DISEASE
KW  - SUSCEPTIBILITY
KW  - MORTALITY
KW  - POLYMORPHISMS
KW  - PHOSPHORYLATION
KW  - EPIDEMIOLOGY
N2  - Background Sepsis continues to be a major cause of death, disability; and health-care expenditure worldwide. Despite evidence suggesting that host genetics can influence sepsis outcomes, no specific loci have yet been convincingly replicated. The aim of this study was to identify genetic variants that influence sepsis survival. Methods We did a genome-wide association study in three independent cohorts of white adult patients admitted to intensive care units with sepsis, severe sepsis, or septic shock (as defined by the International Consensus Criteria) due to pneumonia or intra-abdominal infection (cohorts 1-3, n=2534 patients). The primary outcome was 28 day survival. Results for the cohort of patients with sepsis due to pneumonia were combined in a meta-analysis of 1553 patients from all three cohorts, of whom 359 died within 28 days of admission to the intensive-care unit. The most significantly associated single nucleotide polymorphisms (SNPs) were genotyped in a further 538 white patients with sepsis due to pneumonia (cohort 4), of whom 106 died. Findings In the genome-wide meta-analysis of three independent pneumonia cohorts (cohorts 1-3), common variants in the PER gene were strongly associated with survival (p=9.7x10(-8)). Further genotyping of the top associated SNP (rs4957796) in the additional cohort (cohort 4) resulted in a combined p value of 5.6x10(-8) (odds ratio 0.56, 95% CI 0.45-0.69). In a time-to-event analysis, each allele reduced the mortality over 28 days by 44% (hazard ratio for death 0.56, 95% CI 0.45-0.69; likelihood ratio test p=3.4x10(-9), after adjustment for age and stratification by cohort). Mortality was 9.5% in patients carrying the CC genotype, 15.2% in those carrying the TC genotype, and 25.3% in those carrying the TT genotype. No significant genetic associations were identified when patients with sepsis due to pneumonia and intra-abdominal infection were combined. Interpretation We have identified common variants in the PER gene that associate with a reduced risk of death from sepsis due to pneumonia. The PER gene and associated molecular pathways are potential novel targets for therapy or prevention and candidates for the development of biomarkers for risk stratification.
ER  -

RAUTANEN, A.; T.C. MILLS; A.C. GORDON; P. HUTTON; M. STEFFENS; R. NUAMAH; J.D. CHICHE; T. PARKS; S.J. CHAPMAN; E.E. DAVENPORT; K.S. ELLIOTT; J. BION; P. LICHTNER; T. MEITINGER; T.F. WIENKER; M.J. CAULFIELD; C. MEIN; F. BLOOS; I. BOBEK; P. COTOGNI; Vladimír ŠRÁMEK; S. SARAPUU; M. KOBILAY; V.M. RANIERI; J. RELLO; G. SIRGO; Y.G. WEISS; S. RUSSWURM; E.M. SCHNEIDER; K. REINHART; P.A. HOLLOWAY; J.C. KNIGHT; C.S. GARRARD; J. RUSSELL; K.R. WALLEY; F. STUBER; A.V.S. HILL a C.J. HINDS. Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study. \textit{LANCET RESPIRATORY MEDICINE}. OXFORD: ELSEVIER SCI LTD, 2015, roč.~3, č.~1, s.~53-60. ISSN~2213-2600. Dostupné z: https://doi.org/10.1016/S2213-2600(14)70290-5.

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