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A possible association of responsiveness to adrenocorticotropic hormone with specific GRIN1 haplotypes in infantile spasms
Author(s) -
DING YINGXUE,
ZHANG YING,
HE BING,
YUE WEIHUA,
ZHANG DAI,
ZOU LIPING
Publication year - 2010
Publication title -
developmental medicine and child neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.658
H-Index - 143
eISSN - 1469-8749
pISSN - 0012-1622
DOI - 10.1111/j.1469-8749.2010.03746.x
Subject(s) - adrenocorticotropic hormone , haplotype , medicine , endocrinology , candidate gene , glutamate receptor , genotype , receptor , hormone , biology , gene , genetics
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.