Combined Analysis of Interleukin-10 Gene Polymorphisms and Protein Expression in Children With Cerebral Palsy

Lei Xia; Mingjie Chen; Dan Bi; Juan Song; Xiaoli Zhang; Yangong Wang; Dengna Zhu; Qing Shang; Falin Xu; Xiaoyang Wang; Qinghe Xing; Changlian Zhu

doi:10.3389/fneur.2018.00182

Combined Analysis of Interleukin-10 Gene Polymorphisms and Protein Expression in Children With Cerebral Palsy

Front Neurol. 2018 Mar 22:9:182. doi: 10.3389/fneur.2018.00182. eCollection 2018.

Authors

Lei Xia¹, Mingjie Chen², Dan Bi¹, Juan Song¹, Xiaoli Zhang¹, Yangong Wang², Dengna Zhu¹, Qing Shang³, Falin Xu¹, Xiaoyang Wang^{1

4}, Qinghe Xing^{2

5}, Changlian Zhu^{1

6}

Affiliations

¹ Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Institute of Biomedical Science, Children's Hospital, Fudan University, Shanghai, China.
³ Department of Pediatrics, Zhengzhou Children's Hospital, Zhengzhou, China.
⁴ Perinatal Center, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
⁵ Shanghai Center for Women and Children's Health, Shanghai, China.
⁶ Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.

Abstract

Background: Interleukin-10 (IL-10) is an important anti-inflammatory and immunosuppressive cytokine, and it has indispensable functions in both the onset and development of inflammatory disorders. The association between persistent inflammation and the development of cerebral palsy (CP) has attracted much attention.

Objective: The purpose of this study was to investigate whether IL-10 gene polymorphisms and plasma protein expression are associated with CP and to analyze the role of IL-10 in CP.

Methods: A total of 282 CP patients and 197 healthy controls were genotyped for IL-10 polymorphisms (rs1554286, rs1518111, rs3024490, rs1800871, and rs1800896). Among them, 95 CP patients and 93 healthy controls were selected for plasma IL-10 measurement.

Results: The differences in the rs3024490 (p = 0.033) and rs1800871 (p = 0.033) allele frequencies of IL-10 were determined between CP patients and controls. The frequencies of allele and genotype between CP patients with spastic tetraplegia and normal controls of IL-10 polymorphisms showed significant differences for rs1554286, rs151811, rs3024490, rs1800871, and rs1800896 (p_allele = 0.015, 0.009, 0.006, 0.003, and 0.006, p_genotype = 0.039, 0.018, 0.027, 0.012, and 0.03, respectively). The plasma IL-10 protein level in CP patients was higher than normal controls (9.13 ± 0.77 vs. 6.73 ± 0.63 pg/ml, p = 0.017). IL-10 polymorphisms and protein association analysis showed that the TT genotype had higher plasma IL-10 protein levels compared to the GG + GT genotype at rs3024490 (11.14 ± 7.27 vs. 7.44 ± 6.95 pg/ml, p = 0.045, respectively) in CP cases.

Conclusion: These findings provide an important contribution toward explaining the pleiotropic role of IL-10 in the complex etiology of CP.

Keywords: cerebral palsy; cytokine; inflammation; interleukin-10; single nucleotide polymorphisms.