Abstract | BACKGROUND: METHODS: We screened for variations in the promoter and coding region of the MC2R gene in 91 Chinese patients with infantile spasms and 94 controls, using PCR and a direct sequencing method. The frequencies of the genotypes, alleles and reconstructed haplotypes were analyzed in the cases and controls. The association between ACTH responsiveness and genetic variations of the MC2R gene was also assessed. RESULTS: Four single nucleotide polymorphisms (SNPs) were identified in the MC2R promoter, one of which was a novel specimen at position-2 from the transcription start site ATT, -2T > C. Three SNPs (rs1893220, rs2186944 and -2T > C) showed a significant difference between the cases and controls (P < 0.05 for all). The frequency of the common TCCT haplotype carrying four-SNP major alleles was significantly lower in the cases (39%) than in the controls (60%) (P = 0.00003). The homozygous carriers of the TCCT haplotype had a much lower relative risk than the non-carriers (RR = 0.42, 95% CI 0.26-0.70, P = 0.0001). ACTH responsiveness was strongly associated with the TCCT haplotype (P = 0.000082). Compared with non-carriers of the TCCT haplotype, the homozygous and heterozygous carriers were more responsive to ACTH therapy (P = 0.0002; P = 0.0003, respectively). CONCLUSIONS: Our results indicated that the TCCT haplotype in the MC2R promoter is strongly associated with the responsiveness of the ACTH therapy performed on patients with infantile spasms. The polymorphisms of the MC2R promoter might be one important factor that influences the efficacy of ACTH therapy on infantile spasms.
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Authors | Zhan-Li Liu, Bing He, Fang Fang, Cai-Yun Tang, Li-Ping Zou |
Journal | Chinese medical journal
(Chin Med J (Engl))
Vol. 121
Issue 17
Pg. 1627-32
(Sep 05 2008)
ISSN: 0366-6999 [Print] China |
PMID | 19024088
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptor, Melanocortin, Type 2
- Adrenocorticotropic Hormone
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Topics |
- Adrenocorticotropic Hormone
(therapeutic use)
- Female
- Haplotypes
- Humans
- Infant
- Male
- Polymorphism, Single Nucleotide
- Receptor, Melanocortin, Type 2
(genetics)
- Spasms, Infantile
(drug therapy, genetics)
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