Ying-Xue Ding and Ying Zhang contributed equally to this work.
A possible association of responsiveness to adrenocorticotropic hormone with specific GRIN1 haplotypes in infantile spasms
Article first published online: 16 AUG 2010
© The Authors. Journal compilation © Mac Keith Press 2010
Developmental Medicine & Child Neurology
Volume 52, Issue 11, pages 1028–1032, November 2010
How to Cite
DING, Y.-X., ZHANG, Y., HE, B., YUE, W.-H., ZHANG, D. and ZOU, L.-P. (2010), A possible association of responsiveness to adrenocorticotropic hormone with specific GRIN1 haplotypes in infantile spasms. Developmental Medicine & Child Neurology, 52: 1028–1032. doi: 10.1111/j.1469-8749.2010.03746.x
- Issue published online: 7 OCT 2010
- Article first published online: 16 AUG 2010
- PUBLICATION DATA Accepted for publication 7th June 2010. Published online 16th August 2010.
Aim 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.
Method 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 6.4mo, SD 2.7) and 96 healthy individuals (63 males, 33 females; mean age 7.3mo, 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).
Interpretation The results suggest that haplotypes of GRIN1 may influence responsiveness to ACTH. The findings necessitate further study for confirmation.