Objective: Hepatocellular carcinoma (HCC) is a complex disease which associates with both environmental and genetic factors. The purpose of this study was to investigate whether the genetic polymorphisms of UDP-glu...Objective: Hepatocellular carcinoma (HCC) is a complex disease which associates with both environmental and genetic factors. The purpose of this study was to investigate whether the genetic polymorphisms of UDP-glucuronosyltransferase(UGT1A7), an important phase II biotransformation enzyme, and X-ray repair cross-complementing group 1(XRCC1), a pivotal DNA-repair gene, were related to the risk of HCC in Northeast China. Methods: One hundred and thirty six HCC patients and one hundred and thirty six frequency-matched controls were included in this hospital-based case-control study. Genotypes of UGT1A7 and XRCC1 were determined using allele-specific polymerase chain reaction (AS-PCR) and PCR-restriction fragment length polymorphism (RFLP), and for which the odds ratio (OR) with 95% confidence interval (95% CI) were calculated. Results: The proportion of UGT1A7 low enzymatic allele (*2 or *3) was higher in HCC patients than those in controls. The UGT1A7*1/*2 and *3/*3 genotypes were associated with higher HCC risk (OR=2.09, 95%CI: 1.10-3.97; OR=5.67, 95%CI: 1.76-18.30, respectively). The XRCC1 codon 399 Arg/Gln genotype could also elevate HCC risk (OR=2.16, 95% CI 1.29-3.61). In addition to polymorphisms of UGT1A7 and XRCC1, multivariate logistic regression analysis demonstrated that other significant independent factors associated with HCC were HBV infection (OR=68.07, 95%CI: 28.03-165.26), HCV infection (OR=30.97, 95%CI: 8.06-118.94) and family history of HCC (OR=10.62, 95%CI: 2.22-50.77). Conclusion: The study shows that the polymorphisms of UGT1A7 and XRCC1 are associated with HCC risk. Determination of the polymorphisms of UGT1A7 and XRCC1 may provide an important clue to preventive measure against HCC.展开更多
Cdgler-Najjar syndrome type Ⅰ (CN-I) is the most severe type of hereditary unconjugated hyperbilirubinemia. It is caused by homozygous or compound heterozygous mutations of the UDP-glycuronosyltransferase gene (UG...Cdgler-Najjar syndrome type Ⅰ (CN-I) is the most severe type of hereditary unconjugated hyperbilirubinemia. It is caused by homozygous or compound heterozygous mutations of the UDP-glycuronosyltransferase gene (UGT1A1) on chromosome 2q37. Two patients clinically diagnosed with CN-I were examined in this paper. We sequenced five exons and their flanking sequences, specifically the promoter region of UGT1A 1, of the two patients and their parents. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the UGT1A1 gene copy number of one patient. In patient A, two mutations, c.239_245delCTGTGCC (p.Pro80HisfsX6; had not been reported previously) and c.1156G〉T (p.Va1386Phe), were identified. In patient B, we found that this patient had lost heterozygosity of the UGTIA1 gene by inheriting a deletion of one allele, and had a novel mutation c.1253delT (p.Met418ArgfsX5) in the other allele. In summary, we detected three UGTIA 1 mutations in two CN-I patients: c.239_ 245delCTGTGCC (p.Pro80HisfsX6), c.1253delT (p.MeH18ArgfsX5), and c.1156G〉T (p.Va1386Phe). The former two mutations are pathogenic; however, the pathogenic mechanism of c.1156G〉T (p.Va1386Phe) is unknown.展开更多
基金supported by the grant from Department of Education of Liaoning Province, China (No. 2008S232)
文摘Objective: Hepatocellular carcinoma (HCC) is a complex disease which associates with both environmental and genetic factors. The purpose of this study was to investigate whether the genetic polymorphisms of UDP-glucuronosyltransferase(UGT1A7), an important phase II biotransformation enzyme, and X-ray repair cross-complementing group 1(XRCC1), a pivotal DNA-repair gene, were related to the risk of HCC in Northeast China. Methods: One hundred and thirty six HCC patients and one hundred and thirty six frequency-matched controls were included in this hospital-based case-control study. Genotypes of UGT1A7 and XRCC1 were determined using allele-specific polymerase chain reaction (AS-PCR) and PCR-restriction fragment length polymorphism (RFLP), and for which the odds ratio (OR) with 95% confidence interval (95% CI) were calculated. Results: The proportion of UGT1A7 low enzymatic allele (*2 or *3) was higher in HCC patients than those in controls. The UGT1A7*1/*2 and *3/*3 genotypes were associated with higher HCC risk (OR=2.09, 95%CI: 1.10-3.97; OR=5.67, 95%CI: 1.76-18.30, respectively). The XRCC1 codon 399 Arg/Gln genotype could also elevate HCC risk (OR=2.16, 95% CI 1.29-3.61). In addition to polymorphisms of UGT1A7 and XRCC1, multivariate logistic regression analysis demonstrated that other significant independent factors associated with HCC were HBV infection (OR=68.07, 95%CI: 28.03-165.26), HCV infection (OR=30.97, 95%CI: 8.06-118.94) and family history of HCC (OR=10.62, 95%CI: 2.22-50.77). Conclusion: The study shows that the polymorphisms of UGT1A7 and XRCC1 are associated with HCC risk. Determination of the polymorphisms of UGT1A7 and XRCC1 may provide an important clue to preventive measure against HCC.
文摘Cdgler-Najjar syndrome type Ⅰ (CN-I) is the most severe type of hereditary unconjugated hyperbilirubinemia. It is caused by homozygous or compound heterozygous mutations of the UDP-glycuronosyltransferase gene (UGT1A1) on chromosome 2q37. Two patients clinically diagnosed with CN-I were examined in this paper. We sequenced five exons and their flanking sequences, specifically the promoter region of UGT1A 1, of the two patients and their parents. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the UGT1A1 gene copy number of one patient. In patient A, two mutations, c.239_245delCTGTGCC (p.Pro80HisfsX6; had not been reported previously) and c.1156G〉T (p.Va1386Phe), were identified. In patient B, we found that this patient had lost heterozygosity of the UGTIA1 gene by inheriting a deletion of one allele, and had a novel mutation c.1253delT (p.Met418ArgfsX5) in the other allele. In summary, we detected three UGTIA 1 mutations in two CN-I patients: c.239_ 245delCTGTGCC (p.Pro80HisfsX6), c.1253delT (p.MeH18ArgfsX5), and c.1156G〉T (p.Va1386Phe). The former two mutations are pathogenic; however, the pathogenic mechanism of c.1156G〉T (p.Va1386Phe) is unknown.