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Genetic association study of adaptor protein complex 4 with cerebral palsy in a Han Chinese population

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Abstract

Adaptor protein complex 4 (AP-4) plays a key role in vesicle formation, trafficking, and sorting processes that are critical for brain development and function. AP-4 consists of four subunits encoded by the AP4E1, AP4B1, AP4M1, and AP4S1 genes. A number of studies have pointed to the involvement of AP-4–mediated vesicular trafficking pathways in the etiology of cerebral palsy (CP), the most notable of which are the causative mutations that have recently been identified in each of the AP-4 genes in different CP families. We postulated, therefore, that variations in AP-4 genes might influence an indivual’s susceptibility to CP. In the present study, 16 SNPs were genotyped among 517 CP patients and 502 healthy controls from the Han Chinese population. We systematically analyzed the association of the AP4E1, AP4B1, AP4M1, and AP4S1 genes with CP on the basis of clinical characteristics. No significant associations were found between these variants and the overall risk of CP. Subgroup analysis showed that rs1217401 of AP4B1 was significantly associated with CP as a sequela of hypoxic-ischemic encephalopathy (HIE) (CP + HIE) (allele: p = 0.042151; genotype: p = 4.46 × 10−6). Our results indicate that the 16 variants studied in the genes of the four subunits of AP-4 have no detectable effects on the overall susceptibility to CP, but AP4B1 appears to be a susceptibility gene for CP + HIE in the Han Chinese population.

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Acknowledgments

We are grateful to all the participants in this study. This work was supported by a Grant from National Natural Science Foundation of China (No: 90919049, 30971582, 31271152, 81261120400, 61240031), the 973 Program (2011CB504501), the Shanghai Municipal Commission of Science and Technology Program (09DJ1400601), the Health Department of Henan Province (201201002), the Swedish Research Council (VR) and Swedish governmental grants to scientists working in health care (ALF).

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Authors and Affiliations

  1. Children’s Hospital and Institutes of Biomedical Sciences, Fudan University, 130 Dongan Road, Shanghai, 200032, China

    Honglian Wang, Mingjie Chen, Lei Wang, Zhiheng Huang, Lin He & Qinghe Xing

  2. Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200030, China

    Lin He

  3. Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Kangfuqian Street 7, Zhengzhou, 450052, China

    Yiran Xu, Yanyan Sun, Dengna Zhu, Tongchuan Li & Changlian Zhu

  4. Department of Pediatrics, Zhengzhou Children’s hospital, Zhengzhou, 450052, China

    Qing Shang & Caiyun Ma

  5. Center for Brain Repair and Rehabilitation, University of Gothenburg, Göteborg, Sweden

    Changlian Zhu

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  1. Honglian Wang
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Correspondence to Qinghe Xing or Changlian Zhu.

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H. Wang and Y. Xu contributed equally to this work.

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Wang, H., Xu, Y., Chen, M. et al. Genetic association study of adaptor protein complex 4 with cerebral palsy in a Han Chinese population. Mol Biol Rep 40, 6459–6467 (2013). https://doi.org/10.1007/s11033-013-2761-6

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