TY - JOUR
T1 - Leukotriene pathway polymorphisms are associated with altered cysteinyl leukotriene production in children with acute asthma
AU - Bizzintino, Joelene
AU - Khoo, Siew-Kim
AU - Zhang, Guicheng
AU - Martin, Andrew
AU - Rueter, Kristina
AU - Geelhoed, Gary
AU - Goldblatt, Jack
AU - Laing, Ingrid
AU - Le Souef, Peter
AU - Hayden, Catherine
PY - 2009/7
Y1 - 2009/7
N2 - Cysteinyl leukotrienes (cysLTs) are pro-inflammatory mediators with increasing evidence for a role in childhood acute asthma. This study examined the influence of polymorphisms in cysLT pathway genes on urinary leukotriene E4 (uLTE4) levels and clinical status in acute asthmatic children. Children aged 2–16 years were recruited during an asthma attack (n=205). Where possible, asthma severity scores were assigned, ALOX5AP G-336A, ALOX5 G-1708A, LTC4S A-444C and G-1072A, GPX4 C718T, and CYSTLTR1 T927C genotypes were determined and uLTE4 was measured in acute and convalescent samples. uLTE4 levels were higher acutely compared with convalescence (acute GM: 115.7 pg/mg creatinine; 95% CI 88.6–151.1, convalescence GM: 66.4 pg/mg creatinine; 95% CI 51.5–85.6; n=50 paired samples, p=0.003) and paired sample analysis showed genotype-specific effects with significantly increased uLTE4 for LTC4S-444AA (acute GM: 127.9 pg/mg creatinine; 95% CI 91.8–178.3, convalescence GM: 68.2 pg/mg creatinine; 95% CI 50.5–92.0; n=32, p=0.002), LTC4S-1072 GG (acute GM: 126.7 pg/mg creatinine; 95% CI 95.4–168.3, convalescence GM: 78.9 pg/mg creatinine; 95% CI 59.7–104.1; n=39, p=0.019) and CYSLTR1 927 TT/T_ (acute GM: 96.8 pg/mg creatinine; 95% CI 73.8–126.9, convalescence GM: 62.4 pg/mg creatinine; 95% CI 46.8–83.3; n=28, p=0.036) but not AC/CC, GA/AA, or TC/CC/C_, respectively. When we compared the allele frequencies of the CYSLTR1 SNP between asthmatics and non-asthmatics, the 927C allele was found to be a risk allele for asthma (OR=2.13, 95% CI: 1.06–4.26, p=0.033). Genotypes were not associated with acute or convalescent uLTE4 levels alone and neither the SNPs nor uLTE4 correlated with acute asthma severity. Leukotriene pathway gene polymorphisms may influence the magnitude of cysLT production during an attack, yet their influence alone may not be substantial enough to alter the severity of exacerbations.
AB - Cysteinyl leukotrienes (cysLTs) are pro-inflammatory mediators with increasing evidence for a role in childhood acute asthma. This study examined the influence of polymorphisms in cysLT pathway genes on urinary leukotriene E4 (uLTE4) levels and clinical status in acute asthmatic children. Children aged 2–16 years were recruited during an asthma attack (n=205). Where possible, asthma severity scores were assigned, ALOX5AP G-336A, ALOX5 G-1708A, LTC4S A-444C and G-1072A, GPX4 C718T, and CYSTLTR1 T927C genotypes were determined and uLTE4 was measured in acute and convalescent samples. uLTE4 levels were higher acutely compared with convalescence (acute GM: 115.7 pg/mg creatinine; 95% CI 88.6–151.1, convalescence GM: 66.4 pg/mg creatinine; 95% CI 51.5–85.6; n=50 paired samples, p=0.003) and paired sample analysis showed genotype-specific effects with significantly increased uLTE4 for LTC4S-444AA (acute GM: 127.9 pg/mg creatinine; 95% CI 91.8–178.3, convalescence GM: 68.2 pg/mg creatinine; 95% CI 50.5–92.0; n=32, p=0.002), LTC4S-1072 GG (acute GM: 126.7 pg/mg creatinine; 95% CI 95.4–168.3, convalescence GM: 78.9 pg/mg creatinine; 95% CI 59.7–104.1; n=39, p=0.019) and CYSLTR1 927 TT/T_ (acute GM: 96.8 pg/mg creatinine; 95% CI 73.8–126.9, convalescence GM: 62.4 pg/mg creatinine; 95% CI 46.8–83.3; n=28, p=0.036) but not AC/CC, GA/AA, or TC/CC/C_, respectively. When we compared the allele frequencies of the CYSLTR1 SNP between asthmatics and non-asthmatics, the 927C allele was found to be a risk allele for asthma (OR=2.13, 95% CI: 1.06–4.26, p=0.033). Genotypes were not associated with acute or convalescent uLTE4 levels alone and neither the SNPs nor uLTE4 correlated with acute asthma severity. Leukotriene pathway gene polymorphisms may influence the magnitude of cysLT production during an attack, yet their influence alone may not be substantial enough to alter the severity of exacerbations.
KW - Asthma - mechanism
KW - asthma treatment
U2 - 10.1016/j.plefa.2009.05.022
DO - 10.1016/j.plefa.2009.05.022
M3 - Article
C2 - 19524426
SN - 0952-3278
VL - 81
SP - 9
EP - 15
JO - Prostaglandins, Leukotrienes and Essential Fatty Acids
JF - Prostaglandins, Leukotrienes and Essential Fatty Acids
IS - 1
ER -