Correlação da patogênese da leucomalácia periventricular com polimorfismos em genes das citocinas

Abstract

Periventricular leukomalacia is a frequent consequence of hypoxic-ischemic injury. Functional cytokine gene variants that result in altered production of inflammatory (TNF-α, and IL-1β) or anti-inflammatory (IL-10) cytokines may modify disease processes, including periventricular leukomalacia. Objective: The aim of this study was to evaluate if there is a relationship between the two pro-inflammatory polymorphisms (TNF-α-1031T/C and IL-1β-511C/T) and the anti-inflammatory polymorphism IL-10-1082G/A and periventricular leukomalacia risk in newborns with and without this injury. Materials and methods: A case-control study performed at the Neonatal Intensive Care Unit of the Children's Hospital and Maternity of the SJRio Preto Medical School (FAMERP). Fifty preterm and term newborns were examined as index cases and 50 term newborns as controls, of both genders to both groups. DNA was extracted from peripheral blood leukocytes, and the sites that encompassed the three polymorphisms were amplified by Polimerase Chain Reaction-Restriction Fragment Lenght Polymorphism (PCR/RFLP). Results: Gestational age ranged from 25 to 39 weeks, in Case Group, and at Control Group it ranged from 38 to 42.5 weeks (p<0.0001). Statistically significant association was found between TNF-α-1031T/C high expression genotype TC (intermediate productor inflammatory cytokine) (OR, 2.495; 95% CI, 1.10-5.63; p=0.043) as well as between genotypes (TC+CC) (intermediate + high productors inflammatory cytokine) (OR, 2.471; 95% CI, 1.10-5.55; p=0.044) and risk of periventricular leukomalacia. Statistically significant association was found between IL-1β-511C/T high expression genotypes (CT+TT) intermediate + high productors inflammatory cytokine) (OR, 23.120; 95% CI, 1.31-409.4; p=0.003) and risk of periventricular leukomalacia. Statistically significant association between IL-10-1082G/A high expression genotype GG (anti-inflammatory cytokine high productor) (OR, 0.07407; 95% CI, 0.02-0.34; p<0.0001) as well as between IL-10-1082G high expression allele (OR, 0.5098; 95% CI, 0.29-0.91; p=0,030) and periventricular leukomalacia reduced risk was observed. There was a statistically significant association between TC/CT/GA genotypes combination and the risk of periventricular leukomalacia (OR, 6.469; 95% CI, 2.00-20.92; p=0.001). Conclusions: There is evidence of an association between the both TNF-α-1031T/C and IL-1β-511C/T inflammatory polymorphisms and periventricular leukomalacia risk, and an association of the IL-10-1082G/A anti-inflammatory polymorphism and periventricular leukomalacia reduced risk, in this studied newborns population.