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

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

doi:10.1002/ana.21766

Cited by 61 publications

(53 citation statements)

References 53 publications

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“…The genetic influences affecting CP have been the subject of much attention in recent years. [10][11][12]20,21 Several genes have been identified as risk factors, and have been categorized as thrombophilic, cytokine, apolipoprotein E and a group related to cardiovascular physiology and the functioning of the immune system. 21 Among the candidate genes, several SNPs of the MTHFR genes have been investigated either in normal populations or CP patients.…”

Section: Discussionmentioning

confidence: 99%

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Methylenetetrahydrofolate reductase gene polymorphisms and cerebral palsy in Chinese infants

Xiao

Wang

et al. 2010

J Hum Genet

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Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been suggested as being associated with cerebral palsy (CP) but the evidence is uncertain. The purpose of this study was to investigate whether MTHFR gene polymorphisms contribute to the development of CP in Chinese infants. For this study, 169 health controls and 159 infants with CP including 43 cases also suffering from mental retardation (MR) were recruited. Genomic DNA was prepared from venous blood and all five single nucleotide polymorphisms in MTHFR (rs4846049, rs1476413, rs1801131, rs1801133 and rs9651118) were genotyped using TaqMan technology. There were no significant differences in allele or genotype frequencies between the CP patients and controls at any of the five genetic polymorphisms. Subgroup analysis found statistically significant difference in allele and genotype frequencies between cases with both CP and MR (CP + MR) compared with both CP-only cases and controls at rs4846049, rs1476413 and rs1801131. The frequencies of the T alleles of rs4846049, rs1476413 and the G allele of rs1801131 were greater in the CP + MR patients than in the CP-only patients and controls. This study provides the first evidence pointing to a MTHFR gene polymorphism as a potential risk factor for CP combined with MR.

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Section: Discussionmentioning

confidence: 99%

“…6 A mounting body of recent evidence points to genetic influences on the occurrence of CP. This evidence includes familial data, 7 twin studies 8 and specific genetic factors, [9][10][11][12] and indicate that CP may be related to genomic factors, as well as to environmental incursions during brain development.…”

Section: Introductionmentioning

confidence: 97%

Methylenetetrahydrofolate reductase gene polymorphisms and cerebral palsy in Chinese infants

Xiao

Wang

et al. 2010

J Hum Genet

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“…159;162-167 In addition, DNA variants in the IL-6 gene have been associated with sepsis, brain injury and cerebral palsy, specially in preterm neonates. [168][169][170][171] IL-6 mediates its biological functions through the IL-6R. A cleaved form of the IL-6R can be found in biological fluids and tissues.…”

Section: Single Locus Analysis In Fetuses Demonstrates An Associationmentioning

confidence: 99%

14: Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes

Romero¹,

Velez²,

Mazaki‐Tovi³

et al. 2009

American Journal of Obstetrics and Gynecology

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Objective-To determine whether maternal/fetal SNPs in candidate genes are associated with spontaneous preterm labor/delivery. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptStudy Design-A genetic association study was conducted in 223 mothers and 179 fetuses [preterm labor with intact membranes who delivered <37 weeks (PTB)], and 599 mothers and 628 fetuses (normal pregnancy): 190 candidate genes and 775 SNPs were studied. Single locus/ haplotype association analyses were performed; FDR was used to correct for multiple testing (q*=0.15)]. Results-1)The strongest single locus associations with PTB were IL6R (fetus: p=0.000148) and TIMP2 (mother: p=0.000197), remaining significant after correction for multiple comparisons; 2) Global haplotype analysis indicated an association between a fetal DNA variant in IGF2 and maternal COL4A3 (global p=0.004 and 0.007, respectively).Conclusion-A SNP involved in controlling fetal inflammation (IL6R) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix biology approximately doubled the risk of PTB.

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“…Они локализованы как в кодирующих участках гена -эк-зонах, так и в некодирующих интронах и в промотор-ных участках гена [2, 4]. Имеющиеся на сегодняшний день данные позволяют говорить о тесной ассоциа-ции полиморфизмов генов с разнообразной патологи-ей (в том числе поражение ЦНС) и могут использо-ваться как маркеры в диагностике заболеваний [46].…”

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“…По сравнению с генотипом GG, менее распро-страненный генотип СС был связан с повышенным риском ишемического поражения головного моз-га [46]. Ген, кодирующий ИЛ-10, расположен на хро-мосоме 1 (1q31-1q32).…”

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The role of cytokines and their genetic polymorphism in the development of hypoxic-ischemic encephalopathy among full-term newborn children

et al. 2017

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The problem of ischemic brain damage among newborns is still relevant in the modern world. The frequency of occurrence of this pathology among full-term newborns remains at a fairly high level, both in Russia and abroad. Moreover, it has a high mortality rate and the percentage of early childhood disability is 60-70%, participating in the development of such diseases as minimal brain dysfunction, infantile cerebral palsy, epilepsy. According to the World Health Organization, about 20% of children suffer from neuropsychic disorders, whose causes in 65-80% of cases are perinatal brain lesions of hypoxic origin. The article deals with modern concepts of molecular genetic mechanisms of development of hypoxic-ischemic encephalopathy among newborns, as well as issues of classification and conditions under which this pathology develops. The author studied the latest domestic and foreign literature data on the properties and role of pro and anti-inflammatory cytokines, such as IL-1, IL-4, IL-6, IL-8, IL-10, IL-13, TNF-α, which are, according to modern concepts, one of the main links in the pathogenesis of ischemic brain injury. Also, special attention is paid to their genetic polymorphism, since qualitatively or quantitatively the genetically altered molecules of cytokines affect the immune response. Investigation of the level of cytokines and their genetic polymorphism before the onset of clinical symptoms will allow prediction the onset of the disease and preventing the adverse effects of the damage of the central nervous system.

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

Abstract: Our data suggest that a functional polymorphism in the IL-6 gene is a risk factor for CP among term and near-term infants.

Cited by 61 publications

References 53 publications

Methylenetetrahydrofolate reductase gene polymorphisms and cerebral palsy in Chinese infants

Methylenetetrahydrofolate reductase gene polymorphisms and cerebral palsy in Chinese infants

14: Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes

The role of cytokines and their genetic polymorphism in the development of hypoxic-ischemic encephalopathy among full-term newborn children

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