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The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy.

Bi D, Chen M, Zhang X, Wang H, Xia L, Shang Q, Li T, Zhu D, Blomgren K, He L, Wang X, Xing Q, Zhu C - J Neuroinflammation (2014)

Bottom Line: However, subgroup analysis found significant sex-related differences in allele and genotype frequencies.Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837.Furthermore, the genotype has an effect on IL-6 synthesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfu Street, 450052 Zhengzhou, China. xingqinghe@hotmail.com.

ABSTRACT

Background: The relationship between genetic factors and the development of cerebral palsy (CP) has recently attracted much attention. Polymorphisms in the genes encoding proinflammatory cytokines have been shown to be associated with susceptibility to perinatal brain injury and development of CP. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a pivotal role in neonatal brain injury, but conflicting results have been reported regarding the association between IL-6 single nucleotide polymorphisms (SNPs) and CP. The purpose of this study was to analyze IL-6 gene polymorphisms and protein expression and to explore the role of IL-6 in the Chinese CP population.

Methods: A total of 753 healthy controls and 713 CP patients were studied to detect the presence of five SNPs (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL-6 locus. Of these, 77 healthy controls and 87 CP patients were selected for measurement of plasma IL-6 by Luminex assay. The SHEsis program was used to analyze the genotyping data. For all comparisons; multiple testing on each individual SNP was corrected by the SNPSpD program.

Results: There were no differences in allele or genotype frequencies between the overall CP patients and controls among the five genetic polymorphisms. However, subgroup analysis found significant sex-related differences in allele and genotype frequencies. Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837. Plasma IL-6 levels were higher in CP patients than in the controls, and this difference was more robust in full-term male spastic CP patients. Furthermore, the genotype has an effect on IL-6 synthesis.

Conclusions: The influence of IL-6 gene polymorphisms on IL-6 synthesis and the susceptibility to CP is related to sex and gestational age.

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Related in: MedlinePlus

Comparison of genotypes and plasma IL-6 levels in CP patients and controls. (A) The comparison at rs1800796. (B) The comparison at rs2069837. (C) The comparison at rs2066992. Each dot represents one patient and each bar represents the mean value. *P <0.05; Mann-Whitney U-test. CP, cerebral palsy.
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Figure 2: Comparison of genotypes and plasma IL-6 levels in CP patients and controls. (A) The comparison at rs1800796. (B) The comparison at rs2069837. (C) The comparison at rs2066992. Each dot represents one patient and each bar represents the mean value. *P <0.05; Mann-Whitney U-test. CP, cerebral palsy.

Mentions: The mean plasma IL-6 concentration was higher in the CP patients than in the controls, and this difference was more pronounced in males (Figure 1A). Subgroup analysis showed that the IL-6 level was higher in the spastic CP group compared to the control group (Figure 1B). Furthermore, the IL-6 level in the CP patients was related to gestational age and a significant increase was seen in the full-term birth CP patients (Figure 1C). However, the IL-6 level was not changed compared to controls in the CP patients with PVL (Figure 1D). Further statistical analyses stratified by birth weight, birth asphyxia, MR, HIE, and maternal complications such as PIH, TPL, and PROM were also performed but no differences were found (data not shown). Furthermore, the plasma IL-6 levels were different between CP patients with genotypes CC and those with GG at rs1800796 (P = 0.033) (Figure 2A), and the plasma IL-6 levels of genotype CC at rs1800796 (Figure 2A), AA at rs2069837 (Figure 2B), and TT at rs2066992 (Figure 2C) in CP patients were higher than in their respective controls. Therefore, we have sufficient evidence to assume that there is a positive association of the IL-6 gene with the etiology of CP.


The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy.

Bi D, Chen M, Zhang X, Wang H, Xia L, Shang Q, Li T, Zhu D, Blomgren K, He L, Wang X, Xing Q, Zhu C - J Neuroinflammation (2014)

Comparison of genotypes and plasma IL-6 levels in CP patients and controls. (A) The comparison at rs1800796. (B) The comparison at rs2069837. (C) The comparison at rs2066992. Each dot represents one patient and each bar represents the mean value. *P <0.05; Mann-Whitney U-test. CP, cerebral palsy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4060844&req=5

Figure 2: Comparison of genotypes and plasma IL-6 levels in CP patients and controls. (A) The comparison at rs1800796. (B) The comparison at rs2069837. (C) The comparison at rs2066992. Each dot represents one patient and each bar represents the mean value. *P <0.05; Mann-Whitney U-test. CP, cerebral palsy.
Mentions: The mean plasma IL-6 concentration was higher in the CP patients than in the controls, and this difference was more pronounced in males (Figure 1A). Subgroup analysis showed that the IL-6 level was higher in the spastic CP group compared to the control group (Figure 1B). Furthermore, the IL-6 level in the CP patients was related to gestational age and a significant increase was seen in the full-term birth CP patients (Figure 1C). However, the IL-6 level was not changed compared to controls in the CP patients with PVL (Figure 1D). Further statistical analyses stratified by birth weight, birth asphyxia, MR, HIE, and maternal complications such as PIH, TPL, and PROM were also performed but no differences were found (data not shown). Furthermore, the plasma IL-6 levels were different between CP patients with genotypes CC and those with GG at rs1800796 (P = 0.033) (Figure 2A), and the plasma IL-6 levels of genotype CC at rs1800796 (Figure 2A), AA at rs2069837 (Figure 2B), and TT at rs2066992 (Figure 2C) in CP patients were higher than in their respective controls. Therefore, we have sufficient evidence to assume that there is a positive association of the IL-6 gene with the etiology of CP.

Bottom Line: However, subgroup analysis found significant sex-related differences in allele and genotype frequencies.Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837.Furthermore, the genotype has an effect on IL-6 synthesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfu Street, 450052 Zhengzhou, China. xingqinghe@hotmail.com.

ABSTRACT

Background: The relationship between genetic factors and the development of cerebral palsy (CP) has recently attracted much attention. Polymorphisms in the genes encoding proinflammatory cytokines have been shown to be associated with susceptibility to perinatal brain injury and development of CP. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a pivotal role in neonatal brain injury, but conflicting results have been reported regarding the association between IL-6 single nucleotide polymorphisms (SNPs) and CP. The purpose of this study was to analyze IL-6 gene polymorphisms and protein expression and to explore the role of IL-6 in the Chinese CP population.

Methods: A total of 753 healthy controls and 713 CP patients were studied to detect the presence of five SNPs (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL-6 locus. Of these, 77 healthy controls and 87 CP patients were selected for measurement of plasma IL-6 by Luminex assay. The SHEsis program was used to analyze the genotyping data. For all comparisons; multiple testing on each individual SNP was corrected by the SNPSpD program.

Results: There were no differences in allele or genotype frequencies between the overall CP patients and controls among the five genetic polymorphisms. However, subgroup analysis found significant sex-related differences in allele and genotype frequencies. Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837. Plasma IL-6 levels were higher in CP patients than in the controls, and this difference was more robust in full-term male spastic CP patients. Furthermore, the genotype has an effect on IL-6 synthesis.

Conclusions: The influence of IL-6 gene polymorphisms on IL-6 synthesis and the susceptibility to CP is related to sex and gestational age.

Show MeSH
Related in: MedlinePlus