Genetic and physiologic correlates of longitudinal immunoreactive trypsinogen decline in infants with cystic fibrosis identified through newborn screening
Genetic and physiologic correlates of longitudinal immunoreactive trypsinogen decline in infants with cystic fibrosis identified through newborn screening
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DOI：
10.1016/j.jpeds.2006.07.026
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发表时间：
2006-11-01
影响因子：
5.1
通讯作者：
Accurso, Frank J.
中科院分区：
文献类型：
--
作者：
Sontag, Marci K.;Corey, Mary;Accurso, Frank J.
目标。通过诊断方式和基因型探讨婴儿囊性纤维化（CF）血清免疫反应性胰蛋白酶原（IRT）水平下降的时间过程和生理意义，并探讨IRT的遗传力。研究设计。我们研究了317名CF儿童的纵向IRT测量。我们建立了描述IRT下降的统计模型。胰腺疾病的严重程度（轻度或重度）使用CF基因型进行分配，并通过脂肪吸收不良研究在47名婴儿中得到证实。患有严重疾病的婴儿表现出IRT下降，通常在5岁时出现不可检测的水平。患有轻度疾病的婴儿在头2年表现出下降，无症状地接近高于公布标准的水平。IRT与粪便脂肪呈负相关。胎便性肠梗阻（MI）婴儿的IRT值在出生时显著低于新生儿筛查婴儿。在患有严重疾病的兄弟姐妹中，预测IRT值的共同变异比例很高，表明IRT具有遗传性。CF患儿IRT下降的特征。心肌梗死新生儿IRT值降低提示胰腺损伤加重。此外，IRT在严重疾病患者中具有遗传性，提示早期CF胰腺损伤的遗传修饰因子。本研究证明了统计模型定量表型的遗传力。
Objectives. To characterize the time course and physiologic significance of decline in serum immunoreactive trypsinogen (IRT) levels in infants with cystic fibrosis (CF) by mode of diagnosis and genotype, and to examine IRT heritability.Study design. We studied longitudinal IRT measurements in 317 children with CF. We developed statistical models to describe IRT decline. Pancreatic disease severity (Mild or Severe) was assigned using CF genotype and was confirmed in 47 infants through fat malabsorption studies.Results. Infants with severe disease exhibited IRT decline with non-detectable levels typically seen by 5 years of age. Infants with mild disease exhibited a decline in the first 2 years, asymptomatically approaching a level greater than published norms. IRT and fecal fat were inversely correlated. IRT values in infants with meconium ileus (MI) were significantly lower than newborn-screened infants at birth. The high proportion of shared variation in predicted IRT values among sibling pairs with severe disease suggests that IRT is heritable.Conclusions. IRT declines characteristically in infants with CF. Lower IRT values in newborns with MI suggest increased pancreatic injury. Furthermore, IRT is heritable among patients with severe disease suggesting genetic modifiers of early CF pancreatic injury. This study demonstrates heritability of a statistically modeled quantitative phenotype.