Yanamandra Krishna, Boggs Peter, Loggins John, Baier R John
Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.
Pediatr Pulmonol. 2005 May;39(5):426-32. doi: 10.1002/ppul.20182.
IL-10 is an anti-inflammatory cytokine that may have a protective role in acute lung injury. IL-10 expression is affected by a single-nucleotide polymorphism (SNP) located at position -1082 (G to A). The A allele is associated with lower IL-10 production. Low IL-10 production has been linked to the development of BPD. Thus, the IL-10 -1082 SNP may be a genetic risk factor for the development of BPD in the premature newborn. The IL-10 -1082 SNP was determined in 294 (235 African American, 56 Caucasian, and 3 Hispanic) mechanically ventilated very low birth weight (VLBW) infants and compared to outcome (death and/or development of BPD). Differences in groups were analyzed using ANOVA (continuous variables) or chi square (proportions). The frequency of the A allele in our population was 0.62. Thirty-nine (13.3%) infants were homozygous GG, 146 (49.7%) were heterozygous GA, and 109 (37.0%) were homozygous AA. There were no significant differences between genotype groups with respect to ethnic origin, gender, need for surfactant replacement therapy, and isolation of Ureaplasma urealyticum or Mycoplasma hominis from tracheal aspirates at birth. However, AA infants were slightly more mature and of greater birth weight than GA infants (26.9 +/- 0.2 weeks vs. 26.3 +/- 0.2 weeks, P < 0.05, and 940 +/- 22 g vs. 882 +/- 18 g, P < 0.05, respectively). There was no significant effect of the IL-10 -1082 SNP on mortality or the development of BPD (O2 on 28 days or 36 weeks postconceptional age). However, when considered together, the IL-10 -1082 AA/GA genotypes (lower IL-10 production) were associated with a trend toward reduction in risk for the combined outcome of BPD or death (18/39 vs. 80/255, respectively; P = 0.068). The incidence of other complications of prematurity (retinopathy of prematurity, intraventricular hemorrhage, or periventricular leukomalacia) was not different between groups. In conclusion, the IL-10 -1082 G/A SNP does not have a major influence on mortality or the development of BPD in ventilated VLBW infants.
白细胞介素-10是一种抗炎细胞因子,可能在急性肺损伤中发挥保护作用。白细胞介素-10的表达受位于-1082位(G突变为A)的单核苷酸多态性(SNP)影响。A等位基因与较低的白细胞介素-10产生相关。低白细胞介素-10产生与支气管肺发育不良(BPD)的发生有关。因此,白细胞介素-10 -1082 SNP可能是早产新生儿发生BPD的遗传危险因素。对294例(235例非裔美国人、56例白种人、3例西班牙裔)机械通气的极低出生体重(VLBW)婴儿进行白细胞介素-10 -1082 SNP检测,并与转归情况(死亡和/或BPD的发生)进行比较。采用方差分析(连续变量)或卡方检验(比例)分析组间差异。我们研究人群中A等位基因的频率为0.62。39例(13.3%)婴儿为纯合子GG,146例(49.7%)为杂合子GA,109例(37.0%)为纯合子AA。基因型组在种族、性别、是否需要表面活性剂替代治疗以及出生时气管吸出物中解脲脲原体或人型支原体的分离情况方面无显著差异。然而,AA基因型婴儿比GA基因型婴儿稍成熟且出生体重更大(分别为26.9±0.2周对26.3±0.2周,P<0.05;940±22 g对882±18 g,P<0.05)。白细胞介素-10 -1082 SNP对死亡率或BPD的发生(出生后28天或孕龄36周时需吸氧)无显著影响。然而,综合考虑时,白细胞介素-10 -1082 AA/GA基因型(白细胞介素-10产生较低)与BPD或死亡联合转归风险降低趋势相关(分别为18/39对80/255;P = 0.068)。早产其他并发症(早产儿视网膜病变、脑室内出血或脑室周围白质软化)的发生率在组间无差异。总之,白细胞介素-10 -1082 G/A SNP对机械通气的VLBW婴儿的死亡率或BPD的发生没有重大影响。