Genetic susceptibility to viral exposure may increase the risk of cerebral palsy

被引：28

作者：

Djukic, Michael ^{[1
,2
]}

Gibson, Catherine S. ^{[1
,2
,3
]}

MacLennan, Alastair H. ^{[1
]}

Goldwater, Paul N. ^{[2
,5
]}

Haan, Eric A. ^{[3
,5
]}

McMichael, Gai ^{[1
]}

Priest, Kevin ^{[4
]}

Dekker, Gustaaf A. ^{[1
]}

Hague, William M. ^{[1
]}

Chan, Annabelle ^{[4
]}

Rudzki, Zbigniew ^{[7
]}

Van Essen, Phillipa ^{[3
]}

Khong, T. Yee ^{[6
]}

Morton, Mark R. ^{[1
]}

Ranieri, Enzo ^{[3
]}

Scott, Heather ^{[3
]}

Tapp, Heather ^{[8
]}

Casey, Graeme ^{[7
]}

机构：

[1] Univ Adelaide, Discipline Obstet & Gynaecol, Adelaide, SA 5006, Australia

[2] Univ Adelaide, Womens & Childrens Hosp, Dept Microbiol & Infect Dis, Adelaide, SA 5006, Australia

[3] Univ Adelaide, Womens & Childrens Hosp, Dept Med Genet, Adelaide, SA 5006, Australia

[4] Univ Adelaide, Dept Hlth, Epidemiol Branch, Adelaide, SA 5006, Australia

[5] Univ Adelaide, Discipline Paediat, Adelaide, SA 5006, Australia

[6] Womens & Childrens Hosp, Dept Histopathol, Adelaide, SA, Australia

[7] Inst Med & Vet Sci, Div Mol Pathol, Adelaide, SA 5000, Australia

[8] Womens & Childrens Hosp, Dept Haematol & Oncol, Adelaide, SA, Australia

来源：

AUSTRALIAN & NEW ZEALAND JOURNAL OF OBSTETRICS & GYNAECOLOGY | 2009年 / 49卷 / 03期

基金：

英国医学研究理事会;

关键词：

cerebral palsy; interleukin-4; interleukin-6; Toll-like receptor 4; TOLL-LIKE RECEPTOR-4; INTERLEUKIN-6; GENE; PRETERM BIRTH; GESTATIONAL-AGE; ISCHEMIC-STROKE; POLYMORPHISM; CHORIOAMNIONITIS; ASSOCIATION; POPULATION; MUTATIONS;

D O I：

10.1111/j.1479-828X.2009.00999.x

中图分类号：

R71 [妇产科学];

学科分类号：

100211 [妇产科学];

摘要：

Aim: Cytokine polymorphisms may alter the fetal inflammatory response, increasing susceptibility to cerebral palsy (CP). This study investigates associations between selected inflammatory mediator and cytokine gene polymorphisms (Toll-like receptor-4 (TLR-4) Asp299Gly, interleukin-6 G-174C and interleukin-4 C-589T) and CP from 443 CP infants and 883 control infants. Results were correlated with viral nucleic acids in the same samples. Results: At all gestational ages (GA), TLR-4 was associated with a decreased risk of developing CP (homozygous/heterozygous odds ratio (OR) 0.70, 95% confidence interval (CI) 0.50-0.98) and interleukin (IL)-6 was associated with an increased risk of developing hemiplegia (OR 1.38, 95% CI 1.05-1.83). For infants born 32-36 weeks GA, there was a tenfold increase in the risk of quadriplegic CP with homozygous/heterozygous IL-6 (OR 10.42, 95% CI 1.34-80.82). Viral exposure in combination with IL-4 in preterm infants was associated with a fourfold increased risk of quadriplegia (homozygous/heterozygous OR 4.25, 95% CI 1.21-14.95). In very preterm infants, the absence of detectable viral exposure in combination with IL-4 decreased the risk of developing CP (homozygous/heterozygous OR 0.31, 95% CI 0.13-0.76). Conclusion: Polymorphisms in TLR-4 may be associated with a decreased risk of CP. Polymorphisms in IL-6 or IL-4 may act as susceptibility genes, in the presence of viral exposure, for the development of hemiplegic and quadriplegic CP. These associations require confirmation but they suggest a hypothesis for CP causation due to double jeopardy from neurotropic viral exposure and genetic susceptibility to infection.

引用

页码：247 / 253

页数：7

共 29 条

[1]

Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections [J].