新生児生物学ジャーナル

概要

Functional Polymorphism of the Interleukin-1beta Gene Promoter is Associated with Increased Risk for Cerebral Palsy in Mexican Children with Perinatal Hypoxia-Ischemia Antecedents

Sofia Torres-Merino, María del Rocío Thompson-Bonilla, Bertha Alicia León-Chávez, Daniel Martínez-Fong and Juan Antonio González-Barrios

Background: The genetic polymorphism that contributes to the development of infantile cerebral palsy (ICP) after a perinatal hypoxia-ischemia episode remains unknown. Because IL-1? plays a crucial role in the pathogenesis of hypoxic-ischemic encephalopathy, we evaluated whether the interleukin 1, beta (IL-1?) promoter single-nucleotide polymorphisms (SNPs) correlate with the increased risk for ICP following a perinatal hypoxia-ischemia. We assessed -511 C>T and -31 T>C IL-1? SNPs known to be involved in IL-1? expression.

Methods: Genomic DNAs were purified from peripheral leukocytes of 48 ICP patients and 57 healthy children, amplified by using polymerase chain reaction (PCR), and then analyzed by using the restriction-fragment-length polymorphism technique. The SNP genotypes were established using real time PCR and validated with the restriction enzymes AvaI for -511C-T and AluI for -31T-C in Restriction fragment length polymorphism (RFLP) analysis.

Results: Allelic frequencies of the IL-1? -511 T carrier in patients were significantly higher when compared with those determined in healthy controls. The -511 TT genotype frequency showed a significant difference [odds ratio = 2.4 (95% confidence interval 1.7-3.5), P = 0.0001, and relative risk = 1.5 (95% confidence interval 1.3-1.7)] between patients and controls. The SNP frequencies of -31 genotypes in cerebral palsy patients were not statistically different from the healthy controls.

Conclusions: Mexican children with the homozygous TT mutation in the -511 SNP of the IL-1? gene promoter are 2.4 times more susceptible to develop ICP after suffering perinatal asphyxia than healthy children and the presence of a single allele C could be considered as a genetic protective factor.