title: A possible association of responsiveness to adrenocorticotropic hormone with specific GRIN1 haplotypes in infantile spasms.
abstract: OBJECTIVE
  Adrenocorticotropic hormone (ACTH) has been used as the major therapy for infantile spasms since 1958 because it effectively suppresses seizures; it also normalizes the electroencephalogram in the short-term treatment of infantile spasms. G protein-regulated inducer of neurite outgrowth 1 (GRIN1, also known as N-methyl-D-aspartate receptor 1, NMDAR1), a glutamate receptor, is the main component of functional N-methyl-D-aspartic acid receptors that are involved in the glucocorticoid-induced neuronal damage. Thus, it may be a candidate gene to be tested for responsiveness to ACTH in infantile spasms. In the present study, polymorphisms in the GRIN1 gene in infantile spasms were investigated using a case-control design.
  
  
  METHODS
  Twelve single nucleotide polymorphisms in the GRIN1 gene were genotyped in a Chinese case-control set consisting of 97 unrelated patients with infantile spasms (60 males, 37 females; mean age 6.4 mo, SD 2.7) and 96 healthy individuals (63 males, 33 females; mean age 7.3 mo, SD 3.8). Association analysis was performed on the genotyped data.
  
  
  RESULTS
  Five estimated haplotypes with a frequency of more than 3% were detected. Results of the study showed that responsiveness to treatment with ACTH in homozygous carriers of the CTA haplotype was higher than that in heterozygous carriers and non-carriers (p=0.022). Furthermore, CTG, a rare haplotype, was strongly associated with infantile spasms (p=0.013).
  
  
  CONCLUSIONS
  The results suggest that haplotypes of GRIN1 may influence responsiveness to ACTH. The findings necessitate further study for confirmation.
authors: Department of Neurology, Beijing Children's Hospital, The Capital Medical University, Beijing, China.
authors: Ying-Xue
authors: YX
authors: Ding
authors: Ying
authors: Y
authors: Zhang
authors: Bing
authors: B
authors: He
authors: Wei-Hua
authors: WH
authors: Yue
authors: Dai
authors: D
authors: Zhang
authors: Li-Ping
authors: LP
authors: Zou
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D013036:Spasms, Infantile / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; C485668:GRIN1 protein, human; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D000324:Adrenocorticotropic Hormone