Analysis of single nucleotide polymorphisms in the melanocortin-4 receptor promoter in infantile spasms

Infantile spasms is a severe epileptic encephalopathy of infancy. ACTH that ameliorates infantile spasms might act through activating the central melanocortin-4 receptor (MC4R) to suppress excessive production of corticotrophin-releasing hormone (CRH). This study aimed to elucidate an association between the genetic variants of the MC4R gene and infantile spasms.

The study population comprised 96 patients with infantile spasms and 118 controls. All subjects were screened for variations in the promoter and coding region of the MC4R gene using a direct sequencing method. ATCH responses in patients carrying different genotypes were also assessed.

The distributions of genotypes and alleles of rs11872992 in the MC4R promoter were significantly different between cases and controls. The frequencies of heterozygous carriers (TC genotype) were significantly lower in cases (10%) than in controls (27%) (p=0.003). The distributions of rs11872992 TC and CC genotypes were significantly different between ACTH responders and non-responders (OR, 0.14; 95% C.I, 0.03-0.69; p=0.007). The T-allele carriers (83.3%) had a higher responsiveness to ACTH than non-carriers (41.7%).

The present study shows that genetic variants in the MC4R promoter are associated with the development of infantile spasms. The rs11872992 polymorphism influences ACTH treatment responses in patients with infantile spasms.