Biomedical subjects

Fumin Shen

Publications and source records attributed to Fumin Shen.

8 recordsLinked to original sources

PubMed2007

A haplotype-linkage analysis method for estimating recombination rates using dense SNP trio data.

Meiotic recombination is an important evolution force in shaping human genomes and creating human diversity. Recent explorations suggest that meiotic recombination events tend to happen in certain regions of the genome, leading to the hypothesis of recombination hot spots. To identify such hot spots, we describe an empirical method for estimating the recombination rate, which reflects both historical and current meiotic events, using unphased genotypes from nuclear families, in particular, parents-child trios. The key idea is that use of the haplotypic polymorphisms with multiple adjacent SNPs will increase the number of informative meioses and hence would improve the power of linkage analysis. Since haplotypes of individuals are not directly observed, e.g., in HapMap data, we infer the haplotypes simultaneously while estimating recombination rate. We refer this described method as haplotype-linkage (HALIN) method. Our simulation results show that HALIN gives unbiased estimates of recombination rate. We apply HALIN to analyze the genotype data of chromosome 20 from HapMap data and compare the results to the results using two existing methods, Bayesian coalescent method described by McVean et al. [2004] science 304:581-584 and empirical method by Clarke and Cardon ([2005] Genetics). Results suggest that HALIN identified 75 hot spots on chromosome 20, and 85% of them are also identified by the method by McVean et al. ([2004] science 304:581-584), in addition to a few new hot spots. In comparison with Clarke and Cardon's result, estimated recombination rates (RRs) under these 75 hot spots are significantly greater than those outside of hot spots, which support the general consistency in discovering recombination hot spots between two methods.

Child↗

PubMed2006

Past HBV viral load as predictor of mortality and morbidity from HCC and chronic liver disease in a prospective study.

BACKGROUND AND AIMS: In a prospective cohort study with 11 yr of follow-up, we assessed the relationship between past hepatitis B virus (HBV) viral load and mortality. Surviving cohort members were evaluated for current liver disease. METHODS: We measured HBV viral load by real-time polymerase chain reaction on stored samples from cohort entry (1992-1993) in 2,763 hepatitis B surface antigen (HBsAg)-positive adults. Major end points were death from hepatocellular carcinoma (HCC) or chronic liver disease (CLD). There were 447 deaths. In the 1,683 survivors, we assessed severity of liver disease on a return visit in 2003. Viral load was divided into three categories: undetected (<1.6 x 10(3) copies/mL); low titer (<10(5) copies/mL); and high titer (> or =10(5) copies/mL). RESULTS: For HCC, there was a significant increase in mortality across viral load categories (p(trend) < 0.001). Compared to the HBV undetected category, the relative risk (RR) for HCC mortality in the low viral load group was 1.7 (95% confidence interval [CI] 0.5-5.7) and 11.2 (3.6-35.0) in the high viral load group. For CLD mortality, the RRs were 1.5 (0.2-12.1) and 15.2 (2.1-109.8), respectively (p(trend) < 0.001). The RR associated with high viral load did not change with increased follow-up time. In surviving cohort members evaluated for liver disease in 2003, there was also a significant association of viral load with disease severity. CONCLUSION: In this prospective study, viral load is associated with increased mortality from HCC and CLD in HBV-infected subjects. Viral load may be a useful prognostic tool in HBV infection, and interventions aimed at its reduction should be explored.

Adult↗

PubMed2005

Chronic hepatitis B virus infection and mortality from non-liver causes: results from the Haimen City cohort study.

BACKGROUND: Studies of chronic hepatitis B virus (HBV) infection in endemic populations have rarely documented causes of mortality other than liver disease and hepatocellular carcinoma (HCC). METHODS: We analysed all-cause mortality related to HBV infection, focusing on the deaths not related to liver disease in a prospective cohort of adults living in Haimen City, China, who were followed from 1992 to 2002. Death certificate data from 4590 deaths among 83 794 individuals were analysed. At cohort entry, 15.0% of the 58 454 male subjects and 10.7% of 25 340 female subjects were hepatitis B surface antigen positive [HbsAg(+)]. HCC and chronic liver disease were the major causes of death in both men and women in this population. The analysis focused on non-liver causes of death. RESULTS: When liver-related causes of death were excluded, there was still a significantly higher age-adjusted death rate among HBsAg(+) individuals. The relative risks (RRs) and 95% confidence intervals (CIs) for all non-liver deaths among HBsAg(+) subjects were 1.2 (1.1-1.3) in men and 1.4 (1.1-1.7) in women. Non-liver causes were further subdivided into cancer and non-cancer groups. For all non-liver cancers, the RR was 1.2 (1.0-1.4) for males and 1.7 (1.2-2.3) for females. Non-liver, non-cancer deaths had RRs of 1.2 (1.1-1.4) and 1.2 (0.9-1.6) in males and females, respectively. CONCLUSIONS: HBV-infected individuals may be at increased mortality risk from non-liver causes. Possible reasons include a direct effect of HBV infection, changes in the host immune system as a cause or effect of chronic infection, and behavioural factors associated with HBV infection. Further studies are needed to confirm this finding.

Adult↗

PubMed2004

Hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in chronic carriers.

The role of quantitative viral load in development of hepatocellular carcinoma (HCC) among chronic hepatitis B virus (HBV) carriers was evaluated using real-time PCR (TaqMan PCR), a highly sensitive method for quantitative detection of HBV DNA. Serum samples collected at study entry from HCC cases and matched controls were chosen separately from ongoing prospective cohort studies in Senegal, West Africa, and Haimen City, China. For 14 HCC cases and 28 controls from Senegal, the relative risk (RR, 95% CI) of HCC was 15.6 (2.0-124.3) for those positive by the TaqMan PCR assay. Average length of follow-up (study entry to death from HCC) among cases was 2.8 (+/-1.6) years. The paired median difference between cases and controls was 3.8 x 10(4) virions/ml, with cases higher (P = 0.09). In order to clarify the relationship with lower-titer viremia, we selected 55 cases and 55 matched controls from the Chinese cohort all negative for serum HBV DNA by conventional dot blot hybridization. In this group, the RR associated with HBV DNA positivity by TaqMan PCR was 3.1 (1.1-9.2), with an average duration of follow-up of 3.3 (+/-2.1) years. The median difference in quantitative viremia between cases and controls was 6.0 x 10(4) virions/ml, with cases higher (P < 0.0001). Increased risk appeared to be confined to subjects with viral loads >2.3 x 10(4) virions/ml. In conclusion, HBV viremia, except perhaps at extremely low levels, is associated with increased risk for HCC in prospective studies of chronic carriers in two disparate populations.

Adult↗

PubMed2002

[Genetic polymorphism of UDP-glucuronosyltransferase 1F and susceptibility to hepatocellular carcinoma].

OBJECTIVE: To study the genetic polymorphisms of UDP-glucuronosyltransferase 1F(UGT1F) and the relationship between polymorphisms and susceptibility to hepatocellular carcinoma (HCC). METHODS: The polymorphisms of UGT1F of 84 patients with HCC and 144 healthy controls were detected by PCR-denaturation gradient gel electrophoresis-sequencing or PCR-single strain conformation polymorphsim-sequencing. RESULTS: Three new single nucleotide polymorphisms(SNP) were found: the first one was a transversion of TrarrG at nucleotide 232; the second one was the transition of ArarrG at nucleotide 528 in exon 1; the last one was the transition of ArarrG at nucleotide 376 in intron 2. Additionally, the polymorphism at nucleotide 754 was proved in this study. The frequencies of genotype and allele of 4 loci in cases and controls were analyzed. Both frequencies of genotype G/G(13.10%) and allele G (29.17%) of position 754 of UGT1F in cases were sig nificantly greater than those in controls (2.78% and 19.44% ) respectively. For other loci, the difference between the two groups were not significant. CONCLUSION: Exons 2-5 of UGT1F are highly conservative, but exon 1 emerges highly polymorphic. And the polymorphism at locus 754 may be related with HCC.

Alleles↗

PubMed2002

[Exclusive identification of gene loci of autosomal dominant nonsyndromic hearing loss].

OBJECTIVE: The purpose is to map related genes of an autosomal dominant nonsyndromic hearing loss kindred. METHOD: Linkage analysis was carried out using screening markers of the 22 reported loci. RESULT: Linkage analysis showed no linkages between pedigree gene and reported loci. CONCLUSION: The autosomal dominant nonsyndromic hearing loss in the kindred may be resulted from a new gene.

Chromosome Mapping↗

PubMed2002

[Risk factors in women with gestational diabetes mellitus].

OBJECTIVE: To identify risk factors for gestational diabetes mellitus (GDM) in women and to study the contribution of family history of type-2 diabetes to the risk for DDM. METHODS: A case-control study was performed in 85 women with GDM and 177 cases controls. Univariate and multivariate logistic regression and log-linear model were used to identify risk factors of GDM. RESULTS: Multivariate logistic regression showed that obesity before pregnancy, family history of type-2 diabetes, birth weight of pregnant women, age, fasting plasma level of triglyceride, physical inactivity, etc. all were risk factors for GDM. Analysis with log-linear model showed that parents' (father's or mother's) history of type-2 diabetes associated with GDM, with P-values of 0.012 and 0.017, respectively. Prevalence of diabetes in the mothers of proband with GDM was 9.41%, as compared with that in the fathers of proband with GDM 8.24%, with no statistical significance. CONCLUSIONS: Obesity before gestation, family history of type-2 diabetes, low birth weight of mother, age, increased fasting plasma level of triglyceride, as well as parents' history of type-2 diabetes, all were risk factors for GDM. Physical exercise was found to be a protective factor for GDM. Mother's history of type-2 diabetes did not differ from father's in contributing to the onset of GDM in their offspring.

Adult↗

PubMed2002

[A study on the genetic epidemiology of hepatocellular carcinoma].

OBJECTIVE: To explore the interaction between inheritance and environment with the aid of research on the genetic modes of hepatocellular carcinoma (HCC). METHODS: A genetic epidemiological study of HCC was conducted based on the methods of Penrose, simple segregation and Falconer for 100 proband pedigrees from HBsAg positive cohort. The proband samples came from a cohort of 90,00 people who were followed for 8 years. Analyses on genetic modes were carried out and heritability was calculated through the comparison of the proband pedigrees incidence frequency with incidence frequencies of the cohort and general population. RESULTS: The incidence frequency of first-degree relatives was 4.0%, higher than what was seen in the general population incidence frequency (0.44%) and the cohort (1.03%). A familial aggregation of HBsAg carriers and a strong positive correlation between HBsAg carrier status and HCC were noticed (OR = 8.44, 95% CI: 3.37-20.06, P < 0.001). A ratio of the incidence frequency among siblings to the incident frequency among general population (s/q) approached 1/q(1/2) by Penrose method, but simple segregation did not show agreement with single-gene inheritance. The heritability from positive cohort was 42% +/- 6% (P < 0.05), compared with the heritability (59% +/- 7%) of general population. When the effect of the HBsAg was under control, the heritability from positive cohort turned to be 29% +/- 8% (P < 0.05), compared with the heritability (47% +/- 7%) of general population. CONCLUSION: Our findings suggested that HCC followed a multifactorial mode rather than single inheritance. An interaction effect of inheritance and environment on HCC was also noticed.

Carcinoma, Hepatocellular↗