A possible association of responsiveness to adrenocorticotropic hormone with specific GRIN1 haplotypes in infantile spasms.

Abstract

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 6.4 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).

INTERPRETATION:

The results suggest that haplotypes of GRIN1 may influence responsiveness to ACTH. The findings necessitate further study for confirmation.

• Authors: Ying-Xue Ding, Ying Zhang, Bing He, Wei-Hua Yue, Dai Zhang, Li-Ping Zou
• Journal: Developmental medicine and child neurology (Dev Med Child Neurol) Vol. 52 Issue 11 Pg. 1028-32 (Nov 2010) ISSN: 1469-8749 [Electronic] England
• PMID: 20722663 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Authors. Journal compilation © Mac Keith Press 2010.

Chemical References

• Carrier Proteins
• GRIN1 protein, human
• Nerve Tissue Proteins
• Receptors, N-Methyl-D-Aspartate
• Adrenocorticotropic Hormone

Topics

• Adrenocorticotropic Hormone (therapeutic use)
• Carrier Proteins (genetics)
• Case-Control Studies
• Female
• Gene Frequency
• Genome-Wide Association Study
• Haplotypes (genetics)
• Humans
• Infant
• Male
• Nerve Tissue Proteins (genetics)
• Polymorphism, Single Nucleotide (genetics)
• Receptors, N-Methyl-D-Aspartate (genetics)
• Spasms, Infantile (drug therapy, genetics)
• Treatment Outcome