A polymorphic mutation, c.-3279T>G, in the UGT1A1 promoter is a risk factor for neonatal jaundice in the Malay population.

The uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene encodes the enzyme responsible for bilirubin glucuronidation. To evaluate the contribution of UGT1A1 promoter mutations to neonatal jaundice, we determined the genotypes of c.-3279T>G, c.-3156G>A, and A(TA)7TAA in Malay infants with neonatal jaundice (patients) and in infants without neonatal jaundice (controls). In our population study, only c.-3279T>G was associated with neonatal jaundice. The genotype distributions between both groups were significantly different (p = 0.003): the frequency of homozygosity for c.-3279G was much higher in patients than those in controls. Allele frequency of c.-3279G was significantly higher in patients than those in controls (p = 0.006). We then investigated changes in transcriptional activity because of c.-3279T>G. Luciferase reporter assay in HepG2 cells demonstrated that transcriptional activity of the c.-3279G allele was significantly lower than that of the c.-3279T allele in both the absence and presence of bilirubin. Luciferase reporter assay in COS-7 cells elucidated that c.-3279T>G modified the synergistic effects of the nuclear factors associated with transcriptional machinery. In conclusion, the c.-3279T>G mutation in the UGT1A1 promoter is a genetic risk factor for neonatal jaundice.

Identification of N-acetyl Proline-Glycine-Proline (acPGP) in human serum of adults and newborns by liquid chromatography-tandem mass spectrometry.

BACKGROUND: N-acetyl Proline-Glycine-Proline (acPGP) is a novel neutrophil chemoattractant. However, no studies have been reported to identify the presence of acPGP in human serum. The purpose of our study was to establish a method for measuring acPGP, and to determine whether acPGP is present in human serum. METHODS: Serum samples were obtained from 22 healthy adults and 26 term and preterm newborns. For the sensitive analysis of acPGP, we utilized liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a multiple reaction monitoring (MRM) positive ion mode. RESULTS: The major product ions of acPGP ([M+H](+) ion, m/z 312) appeared at 112 and 140. The MRM (transition: m/z 312/112) chromatogram in human serum showed a single peak with the same retention time as that of authentic acPGP. The calibration curve of authentic acPGP was linear, and our quantitative results indicated high precision. The mean serum acPGP levels in adults and newborns were 6.3 and 18.7 pg/ml, respectively. In newborns, lower birth weight infants had significantly higher serum acPGP levels. CONCLUSIONS: We established a method for the quantification of serum acPGP using LC-MS/MS, and this paper provides the first evidence for the presence of acPGP in human serum of adults and newborns.