A possible association of responsiveness to adrenocorticotropic hormone with specific GRIN1 haplotypes in infantile spasms.
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.
Ding
Ying-Xue
YX
Department of Neurology, Beijing Children's Hospital, The Capital Medical University, Beijing, China.
Zhang
Ying
Y
He
Bing
B
Yue
Wei-Hua
WH
Zhang
Dai
D
Zou
Li-Ping
LP
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
D002352:Carrier Proteins; C485668:GRIN1 protein, human; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D000324:Adrenocorticotropic Hormone