No abstract

The potential for genetic variation to modulate neonatal hyperbilirubinemia risk is increasingly being recognized. A case-control study was designed to assess comprehensive contributions of the multiple genetic modifiers of bilirubin metabolism on significant neonatal hyperbilirubinemia in Chinese descendents. Eleven common mutations and polymorphisms across five bilirubin metabolism genes, namely those encoding UGT1A1, HMOX1, BLVRA, SLCO1B1 and SLCO1B3, were determined using the high resolution melt (HRM) assay or PCR-capillary electrophoresis analysis. A total of 129 hyperbilirubinemic infants and 108 control subjects were evaluated. Breastfeeding and the presence of the minor A allele of rs4148323 (UGTA*6) were correlated with an increased risk of hyperbilirubinemia (OR=2.17, P=0.02 for breastfeeding; OR=9.776, P=0.000 for UGTA*6 homozygote; OR=3.151, P=0.000 for UGTA*6 heterozygote); whereas, increasing gestational age and the presence of –TA7 repeat variant of UGT1A1 decreased the risk (OR=0.721, P=0.003 for gestational age; OR=0.313, P=0.002 for heterozygote TA6/TA7). In addition, the SLCO1B1 and SLCO1B3 polymorphisms also contributed to an increased risk of hyperbilirubinemia. This detailed analysis revealed the impact of multiple genetic modifiers on neonatal hyperbilirubinemia. This may support the use of genetic tests for clinical risk assessment. Furthermore, the established HRM assay can serve as an effective method for large-scale investigation.

In this study, we characterized the concentration of heavy metals in PM 2.5 in the community with e-waste dismantling, Guiyu, China and assessed potential public health risk associated with heavy metal composition of PM 2.5 for local residents. Daily samples of PM 2.5 were collected with Harvard Impactors on the roof of 3-story buildings from March 2012-April 2013 in Guiyu (n = 133) and seasonal samples were collected in a reference site, Haojiang (n = 33). The concentrations of PM 2.5 mass and heavy metals were analyzed gravimetrically and by graphite furnace atomic absorption spectrometry, respectively. The geometric mean concentrations of PM 2.5 , Pb and Cd in Guiyu were higher than in the reference area (PM 2.5 : 49.9 µg m -3 vs. 37.6 , p < 0.01; Pb: 160 ng m -3 vs. 69 ng m vs. 16 ng m -3 , p > 0.05). The metal concentrations in PM 2.5 from Guiyu were also higher when compared to other Asian cities. We observed higher heavy metal concentrations during winter and spring than summer and fall. Human health risk assessment showed that the total potential cancer risk for both adults and children are higher than the safe acceptable range recommended by the US EPA. Furthermore, the carcinogenic and non-carcinogenic elements in PM 2.5 pose higher public health risk to children than adults. The results indicate that air pollution emitted from informal e-waste recycling activities might be affecting the health of local residents, especially children.

Besides G6PD-deficiency screening, UGT1A1 genetic analysis, and especially the UGT1A1*6(c.211G>A, p.Arg71Gly) polymorphism detection, may be taken into consideration for early diagnosis and treatment of severe hyperbilirubinemic newborns in southern China.