Genetic association study of adaptor protein complex 4 with cerebral palsy in a Han Chinese population.
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.
Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 130 Dongan Road, Shanghai, 200032, China, honglian198410@163.com.
Honglian
H
Wang
Yiran
Y
Xu
Mingjie
M
Chen
Qing
Q
Shang
Yanyan
Y
Sun
Dengna
D
Zhu
Lei
L
Wang
Zhiheng
Z
Huang
Caiyun
C
Ma
Tongchuan
T
Li
Lin
L
He
Qinghe
Q
Xing
Changlian
C
Zhu
D033964:Adaptor Protein Complex 4 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002547:Cerebral Palsy / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D033964:Adaptor Protein Complex 4