Blood immunoreactive trypsinogen concentrations are genetically determinedin healthy and cystic fibrosis newborns

Newborns with cystic fibrosis (CF) have increased blood immunoreactive tryp sinogen concentrations. When screening for GF in the newborn by immunoreact ive trypsinogen measurement, an abnormally high proportion of healthy Delta F508 carriers is found among false-positive neonates, suggesting that a re lationship could exist between immunoreactive trypsinogen concentration at birth and the genetic status. Therefore, this study analysed the possible r elationships between neonatal blood immunoreactive trypsinogen concentratio ns and genotype in 1842 healthy newborns and 111 CF patients detected by a neonatal screening programme. A close correlation was found between immunor eactive trypsinogen and Delta F508: the probability of a healthy newborn be ing a carrier of this mutation increased regularly with the neonatal immuno reactive trypsinogen concentration. In CF patients, there was a significant difference between Delta F508 homozygotes and Delta F508/X (X =other mutat ion) compound heterozygotes with respect to the mean neonatal blood immunor eactive trypsinogen concentration. CF neonates with two mutations affecting the nucleotide binding domains of the cystic fibrosis transmembrane conduc tance regulator protein had significantly higher mean immunoreactive trypsi nogen concentrations than patients with one mutation affecting a membrane-s panning domain. The data strongly suggest that the neonatal immunoreactive trypsinogen concentration is, in part, genetically determined, with a wide range of variations, similar to the features which have been shown for the relations between the genotype and clinical phenotypes of CF patients.