Interleukin-6 genotype and risk for cerebral palsy in term and near-term infants

Yvonne W. Wu, Lisa A. Croen, Anthony R. Torres, Judith A Van de Water, Judith K. Grether, Nathaniel N. Hsu

Research output: Contribution to journalArticle

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Abstract

Objective: Chorioamnionitis is associated with increased risk for cerebral palsy (CP) in term infants. A functional polymorphism in the interleukin-6 (IL-6) gene has been implicated in newborn brain injury. We studied whether the IL-6-174 G/C polymorphism confers increased risk for CP in term infants. Methods: This population-based case-control study included 334,333 live-born infants born at ≥36 weeks gestation within Kaiser Permanente Medical Care Program from 1991 to 2002. Case patients (n = 250) were identified from electronic records and confirmed by chart review, and comprised all infants with spastic or dyskinetic CP not caused by developmental abnormalities who had a neonatal blood specimen available for study. Control patients (n = 305) were randomly selected from the study population. Results: Compared with genotype GG, the less common CC genotype was associated with increased risk for overall CP (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.6), quadriparetic CP (OR, 4.1; 95% CI, 1.8-9.3), and hemiparetic CP (OR, 2.7; 95% CI, 1.3-5.7), after controlling for race. The C allele conferred increased risk for CP in both recessive and additive genetic models. In multivariate analysis controlling for race, independent risk factors for CP included CC genotype compared with GG (OR, 2.4; 95% CI, 1.3-4.4), clinical chorioamnionitis (OR, 4.6; 95% CI, 2.1-10.4), maternal age ≥ 35 (OR, 2.6; 95% CI, 1.6-4.1), and male sex (OR, 1.6; 95% CI, 1.1-2.4). Interpretation: Our data suggest that a functional polymorphism in the IL-6 gene is a risk factor for CP among term and near-term infants.

Original languageEnglish (US)
Pages (from-to)663-670
Number of pages8
JournalAnnals of Neurology
Volume66
Issue number5
DOIs
StatePublished - 2009

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Cerebral Palsy
Interleukin-6
Genotype
Odds Ratio
Confidence Intervals
Chorioamnionitis
Genetic Models
Sex Ratio
Maternal Age
Brain Injuries
Population
Genes
Case-Control Studies
Multivariate Analysis
Alleles
Newborn Infant
Pregnancy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Interleukin-6 genotype and risk for cerebral palsy in term and near-term infants. / Wu, Yvonne W.; Croen, Lisa A.; Torres, Anthony R.; Van de Water, Judith A; Grether, Judith K.; Hsu, Nathaniel N.

In: Annals of Neurology, Vol. 66, No. 5, 2009, p. 663-670.

Research output: Contribution to journalArticle

Wu, Yvonne W. ; Croen, Lisa A. ; Torres, Anthony R. ; Van de Water, Judith A ; Grether, Judith K. ; Hsu, Nathaniel N. / Interleukin-6 genotype and risk for cerebral palsy in term and near-term infants. In: Annals of Neurology. 2009 ; Vol. 66, No. 5. pp. 663-670.
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abstract = "Objective: Chorioamnionitis is associated with increased risk for cerebral palsy (CP) in term infants. A functional polymorphism in the interleukin-6 (IL-6) gene has been implicated in newborn brain injury. We studied whether the IL-6-174 G/C polymorphism confers increased risk for CP in term infants. Methods: This population-based case-control study included 334,333 live-born infants born at ≥36 weeks gestation within Kaiser Permanente Medical Care Program from 1991 to 2002. Case patients (n = 250) were identified from electronic records and confirmed by chart review, and comprised all infants with spastic or dyskinetic CP not caused by developmental abnormalities who had a neonatal blood specimen available for study. Control patients (n = 305) were randomly selected from the study population. Results: Compared with genotype GG, the less common CC genotype was associated with increased risk for overall CP (odds ratio [OR], 2.6; 95{\%} confidence interval [CI], 1.5-4.6), quadriparetic CP (OR, 4.1; 95{\%} CI, 1.8-9.3), and hemiparetic CP (OR, 2.7; 95{\%} CI, 1.3-5.7), after controlling for race. The C allele conferred increased risk for CP in both recessive and additive genetic models. In multivariate analysis controlling for race, independent risk factors for CP included CC genotype compared with GG (OR, 2.4; 95{\%} CI, 1.3-4.4), clinical chorioamnionitis (OR, 4.6; 95{\%} CI, 2.1-10.4), maternal age ≥ 35 (OR, 2.6; 95{\%} CI, 1.6-4.1), and male sex (OR, 1.6; 95{\%} CI, 1.1-2.4). Interpretation: Our data suggest that a functional polymorphism in the IL-6 gene is a risk factor for CP among term and near-term infants.",
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T1 - Interleukin-6 genotype and risk for cerebral palsy in term and near-term infants

AU - Wu, Yvonne W.

AU - Croen, Lisa A.

AU - Torres, Anthony R.

AU - Van de Water, Judith A

AU - Grether, Judith K.

AU - Hsu, Nathaniel N.

PY - 2009

Y1 - 2009

N2 - Objective: Chorioamnionitis is associated with increased risk for cerebral palsy (CP) in term infants. A functional polymorphism in the interleukin-6 (IL-6) gene has been implicated in newborn brain injury. We studied whether the IL-6-174 G/C polymorphism confers increased risk for CP in term infants. Methods: This population-based case-control study included 334,333 live-born infants born at ≥36 weeks gestation within Kaiser Permanente Medical Care Program from 1991 to 2002. Case patients (n = 250) were identified from electronic records and confirmed by chart review, and comprised all infants with spastic or dyskinetic CP not caused by developmental abnormalities who had a neonatal blood specimen available for study. Control patients (n = 305) were randomly selected from the study population. Results: Compared with genotype GG, the less common CC genotype was associated with increased risk for overall CP (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.6), quadriparetic CP (OR, 4.1; 95% CI, 1.8-9.3), and hemiparetic CP (OR, 2.7; 95% CI, 1.3-5.7), after controlling for race. The C allele conferred increased risk for CP in both recessive and additive genetic models. In multivariate analysis controlling for race, independent risk factors for CP included CC genotype compared with GG (OR, 2.4; 95% CI, 1.3-4.4), clinical chorioamnionitis (OR, 4.6; 95% CI, 2.1-10.4), maternal age ≥ 35 (OR, 2.6; 95% CI, 1.6-4.1), and male sex (OR, 1.6; 95% CI, 1.1-2.4). Interpretation: Our data suggest that a functional polymorphism in the IL-6 gene is a risk factor for CP among term and near-term infants.

AB - Objective: Chorioamnionitis is associated with increased risk for cerebral palsy (CP) in term infants. A functional polymorphism in the interleukin-6 (IL-6) gene has been implicated in newborn brain injury. We studied whether the IL-6-174 G/C polymorphism confers increased risk for CP in term infants. Methods: This population-based case-control study included 334,333 live-born infants born at ≥36 weeks gestation within Kaiser Permanente Medical Care Program from 1991 to 2002. Case patients (n = 250) were identified from electronic records and confirmed by chart review, and comprised all infants with spastic or dyskinetic CP not caused by developmental abnormalities who had a neonatal blood specimen available for study. Control patients (n = 305) were randomly selected from the study population. Results: Compared with genotype GG, the less common CC genotype was associated with increased risk for overall CP (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.6), quadriparetic CP (OR, 4.1; 95% CI, 1.8-9.3), and hemiparetic CP (OR, 2.7; 95% CI, 1.3-5.7), after controlling for race. The C allele conferred increased risk for CP in both recessive and additive genetic models. In multivariate analysis controlling for race, independent risk factors for CP included CC genotype compared with GG (OR, 2.4; 95% CI, 1.3-4.4), clinical chorioamnionitis (OR, 4.6; 95% CI, 2.1-10.4), maternal age ≥ 35 (OR, 2.6; 95% CI, 1.6-4.1), and male sex (OR, 1.6; 95% CI, 1.1-2.4). Interpretation: Our data suggest that a functional polymorphism in the IL-6 gene is a risk factor for CP among term and near-term infants.

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