Gabriel Marta Lúcia, Braga Fernanda Braojos, Cardoso Mariana Rodero, Lopes Ana Cláudia, Piatto Vânia Belintani, Souza Antônio Soares
Radiology Department, São José do Rio Preto Medical School, FAMERP, São Paulo, Brazil.
Morphology Department, São José do Rio Preto Medical School, FAMERP, São Paulo, Brazil.
J Inflamm Res. 2016 May 5;9:59-67. doi: 10.2147/JIR.S103697. eCollection 2016.
Periventricular leukomalacia (PVL) is a frequent consequence of hypoxic-ischemic injury. Functional cytokine gene variants that result in altered production of inflammatory (tumor necrosis factor-alpha [TNF-α] and interleukin-1beta [IL-1β]) or anti-inflammatory (interleukin-10 [IL-10]) cytokines may modify disease processes, including PVL.
The aim of this study was to evaluate if there is a relationship between the two proinflammatory polymorphisms (TNF-α-1031T/C and IL-1β-511C/T) and the anti-inflammatory polymorphism IL-10-1082G/A and PVL risk in Brazilian newborns with and without this injury.
A cross-sectional case-control study performed at the Neonatal Intensive Care Unit of the Children's Hospital and Maternity of the São José do Rio Preto Medical School (FAMERP). Fifty preterm and term newborns were examined as index cases and 50 term newborns as controls, of both sexes for both groups. DNA was extracted from peripheral blood leukocytes, and the sites that encompassed the three polymorphisms were amplified by polymerase chain reaction-restriction fragment length polymorphism.
Gestational age ranged from 25 to 39 weeks, in the case group, and in the 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 (odds ratio [OR], 2.495; 95% confidence interval [CI], 1.10-5.63; P=0.043) as well as between genotypes (TC + CC) (OR, 2.471; 95% CI, 1.10-5.55; P=0.044) and risk of PVL. Statistically significant association was found between IL-1β-511C/T high expression genotypes (CT + TT) (OR, 23.120; 95% CI, 1.31-409.4; P=0.003) and risk of PVL. Statistically significant association between IL-10-1082G/A high expression genotype GG (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 PVL reduced risk was observed. There was a statistically significant association between TC/CT/GA genotype combination and the risk of PVL (OR, 6.469; 95% CI, 2.00-20.92; P=0.001).
There is evidence of an association between the polymorphisms TNF-α-1031T/C, IL-1β-511C/T, and IL-10-1082G/A and PVL risk in this Brazilian newborn population studied.
脑室周围白质软化(PVL)是缺氧缺血性损伤的常见后果。导致炎性(肿瘤坏死因子-α [TNF-α] 和白细胞介素-1β [IL-1β])或抗炎性(白细胞介素-10 [IL-10])细胞因子产生改变的功能性细胞因子基因变异可能会改变包括PVL在内的疾病进程。
本研究旨在评估两种促炎多态性(TNF-α -1031T/C和IL-1β -511C/T)以及抗炎多态性IL-10 -1082G/A与巴西有无PVL损伤新生儿的PVL风险之间是否存在关联。
在圣若泽杜里奥普雷图医学院(FAMERP)儿童医院和妇产医院的新生儿重症监护病房进行了一项横断面病例对照研究。两组均检查了50例早产和足月新生儿作为索引病例,50例足月新生儿作为对照,两组均包括男女两性。从外周血白细胞中提取DNA,并通过聚合酶链反应-限制性片段长度多态性扩增包含这三种多态性的位点。
病例组的胎龄为25至39周,对照组的胎龄为38至42.5周(P<0.0001)。发现TNF-α -1031T/C高表达基因型TC(比值比[OR],2.495;95%置信区间[CI],1.10 - 5.63;P = 0.043)以及基因型(TC + CC)(OR,2.471;95% CI,1.10 - 5.55;P = 0.044)与PVL风险之间存在统计学显著关联。发现IL-1β -511C/T高表达基因型(CT + TT)(OR,23.120;95% CI,1.31 - 409.4;P = 0.003)与PVL风险之间存在统计学显著关联。观察到IL-10 -1082G/A高表达基因型GG(OR,0.07407;95% CI,0.02 - 0.34;P<0.0001)以及IL-10 -1082G高表达等位基因(OR,0.5098;95% CI,0.29 - 0.91;P = 0.030)与PVL风险降低之间存在统计学显著关联。TC/CT/GA基因型组合与PVL风险之间存在统计学显著关联(OR,6.469;95% CI,2.00 - 20.92;P = 0.001)。
在本研究的巴西新生儿人群中,有证据表明TNF-α -1031T/C、IL-1β -511C/T和IL-10 -1082G/A多态性与PVL风险之间存在关联。