The incidence of severe neonatal hyperbilirubinemia is higher in Asians than in whites. A case-control study was designed to investigate the effects of eight known risk factors [breast feeding, ABO incompatibility, premature birth, infection, cephalohematoma, asphyxia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and variant UDP-glucuronosyltransferase 1A1 (UGT1A1) gene] and a suspicious analog [organic anion transporter 2 (OATP 2) gene] on severe hyperbilirubinemia in Taiwanese neonates. The 72 study subjects and 100 hospital control subjects consisted of neonates with peak serum bilirubin levels Ն342 M and Ͻ256.5 M, respectively. The PCR-restriction fragment length polymorphism method was applied to detect the UGT1A1, OATP 2, and G6PD genes. Bilirubin is mainly produced in its unconjugated form by the turnover of erythrocytes. It may be transported by the organic anion transporter 2 (OATP 2) (1), and it is then conjugated with glucuronic acid through reaction with UDP-glucuronosyltransferase 1A1 (UGT1A1) in the liver before being excreted into the bile (2). The bilirubin level in neonates is much higher than in adults because the life span of the erythrocytes is relatively short and the capacity for bilirubin elimination is lower than in adults (3). The peak serum levels of unconjugated bilirubin in full-term Asian and American-Indian neonates are double those in white and black populations (4). The incidence of severe hyperbilirubinemia and kernicterus is also higher among newborn Asian infants (3). These findings suggest that genetic factors may be involved in the development of severe neonatal hyperbilirubinemia.Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic defect, affecting Ͼ400 million individuals worldwide (5). Furthermore, G6PD deficiency was the main risk factor for development of severe hyperbilirubinemia in Taiwanese neonates in the past (6). The situation has improved, however, since neonatal G6PD screening tests and health education were instituted at the Cathay General Hospital (CGH) in Taipei and nationwide in Taiwan in 1981 (7) and 1987 (6), respectively. Recently, another genetic defect, a variation in the promoter area or within the coding region of the UGT1A1 gene, was associated with neonatal hyperbilirubinemia in whites and in Japanese and Taiwanese, respectively (8 -12). It has been determined that the A(TA) 7 TAA promoter variant or homozygous G to A variation at nucleotide 211 in

Some variations in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene are involved in the development of unconjugated hyperbilirubinemia. We hypothesize that other genetic factors may also be associated with this disease. A total of 227 adults with normal routine haematology and liver function (apart from bilirubin testing for which they revealed bilirubin > or = 25.7 micromol/l and unconjugated bilirubin/total bilirubin > or = 80%), and 235 sex- and age-matched controls, were recruited. All subjects were analysed for UGT1A1, glucose-6-phosphate dehydrogenase (G6PD) and organic anion transporter polypeptide 2 (OATP2) genotypes using polymerase chain reaction-restriction fragment length polymorphism. The results indicated that G6PD deficiency, variant UGT1A1 gene and variant OATP2 gene were risk factors for hyperbilirubinemia. The odds ratios (OR) (with 95% confidence interval) were 220.83 (34.68-1406.30), 73.61 (17.01-318.63), 45.15 (11.19-182.22), 15.46 (4.35-54.99) and 6.51 (1.83-23.09), respectively, for individuals featuring the common UGT1A1/OATP2 haplotypes homozygous/heterozygous, compound heterozygous/heterozygous, compound heterozygous/wild-type, heterozygous/heterozygous and heterozygous/wild-type variations amongst subjects with normal G6PD activity. Amongst the subjects with G6PD deficiency, the OR was 159.00 (24.57-1028.94) for individuals carrying variations in both UGT1A1 and OATP2 genes. The UGT1A1/OATP2 haplotypes homozygous/wild-type, homozygous/compound heterozygous and homozygous/homozygous for G6PD normal and variant/wild-type for G6PD deficient individuals were only observed in the case group, and not in the control group. Amongst hyperbilirubinemic adults, bilirubin values tended to parallel variation status of their haplotypes. Adults featuring certain haplotypes in UGT1A1, OATP2 and G6PD genes face a high risk of developing unconjugated hyperbilirubinemia.

In conclusion, carriage of the UGT1A7*3 allele, as well as variant-211 UGT1A1 allele represents a risk factor for the development of, and a determinant for, metastases associated with CRC patients.

An inverse dose-response relationship was demonstrated between the detoxifying activity of the UGT1A7 genotypes and HCC. Of the male HCC patients, median onset age for those carrying an UGT1A7 low-activity genotype was 9 yr lower than those bearing the high-activity variant.

"Ham-Hong-Chho" is a folk medicine in Taiwan, derived from the entire plants of Bidens pilosa L. var. minor (Blume) Sherff (Compositae), B. pilosa L. and B. chilensis DC. The anti-inflammatory effect of aqueous extracts of the three plants against paw edema induced by carrageenan and chronic arthritis induced by complete Freund's adjuvant were determined in rats. The results indicated that paw edema induced by carrageenan was significantly decreased by treatment with aqueous extracts (150 or 300 mg/kg) of all three plants (p < 0.05) and that the effect of Bidens pilosa var. minor was the most potent. However, only extracts (500 mg/kg) of B. pilosa L. var. minor and B. pilosa L. significantly decreased the paw edema induced by complete Freund's adjuvant (p < 0.05).