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PubMed2005

Classifying genotype F of hepatitis B virus into F1 and F2 subtypes.

AIM: To explore the propriety of providing hepatitis B virus (HBV) genotypes F and H with two distinct genotypes. METHODS: Eleven HBV isolates of genotype F (HBV/F) were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carried out among them along with HBV isolates previously reported. RESULTS: Seven of them clustered with reported HBV/F isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by > 13.7% from HBV isolates of the other six genotypes (A-E and G). Based on a marked genomic divergence, falling just short of > 8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes (A-E and G), two clusters separated by distinct genetic distances emerged. CONCLUSION: Based on these analyses, classifying HBV/F isolates into two subtypes (F1 and F2) would be more appropriate than providing them with two distinct genotypes (F and H).

Amino Acid Sequence↗
PubMed1996

Hepatitis C genotypes: current trends and future implications.

OBJECTIVE: To review the geographic distribution and current understanding of hepatitis C virus (HCV) genotypes in regard to liver disease activity and response to treatment. MATERIAL AND METHODS: We review the relevant medical literature and discuss our recent findings relative to chronic HCV infection and the importance of HCV genotypes. RESULTS: HCV genotypes 1a and 1b are the most commonly found genotypes in patients with chronic HCV in the United States. Infection with HCV genotype 1b may be associated with more severe liver disease and may have a higher risk for the development of hepatocellular carcinoma. HCV genotype 2b seemed to be the most sensitive and HCV genotype 1b was the least sensitive to interferon therapy. CONCLUSION: The identification of the infectious HCV genotype may be beneficial in clinical settings and may assist in the selection of patients who would benefit from interferon treatment.

Genome, Viral↗
PubMed1997

Genotyping of hepatitis C virus in the Dominican Republic.

Genotyping of hepatitis C virus (HCV) of liver disease patients in the Dominican Republic was performed. Eighty-four samples positive for HCV antibody, which were confirmed by ELISA, particle agglutination, and recombinant immunoblot assay III tests, were subjected to HCV genotyping by polymerase chain reaction using type-specific primers located in the nonstructural protein 5 region. Of the 84 samples tested, 50 (59%) were found to have genotype 1a/I and this genotype was the most frequent type detected in the present study. The numbers of isolates of genotypes 1b/II, 2a/III, 2b/IV, and 3a/V were three (3.6%) six (7.1%), two (2.4%), and two 2.4%), respectively. The number of samples having mixed genotype populations was 16 (19%). The possible causes of the high prevalence of genotype 1a/I in the Dominican Republic compared with other countries and of the high detection ratio of samples having mixed genotypes are discussed.

Agglutination Tests↗
PubMed2003

R/R genotype of human paraoxonase (PON1) is more protective against lipoprotein oxidation and coronary artery disease in Japanese subjects.

Human paraoxonase (PON1) is an high-density lipoprotein (HDL) -associated enzyme that is proposed to protect against the oxidation of lipoproteins. Recently, the association of coronary artery disease (CAD) and PON1 activity was reported. Furthermore, the R/R genotype of PON1 has been related to the risk for CAD. In this study we investigated the PON1 genotype and susceptibility to lipoprotein oxidation to elucidate the contribution of PON1 to atherosclerosis in Japanese subjects. We studied 179 patients who underwent coronary angiography and their PON1 genotypes were determined. Lipoproteins were obtained from a patient's blood after at least 12 hours fasting and were separated with sequential ultracentrifugation. We analyzed the thiobarbituric acid reactive substances (TBARS) and continuously monitored the copper-induced oxidation three genotype groups. Genotype frequencies of Q/Q, Q/R, and R/R were 21.2%, 36.9%, and 41.9%, respectively. PON1 polymorphism clearly determined the lipid oxidation. The R/R genotype of PON1 had significantly lower levels of plasma and HDL TBARS and significantly retarded the initiation of oxidation in HDL and low-density lipoprotein (LDL). The R/R genotype was related to the lower prevalence of CAD. The PON1 genotype clearly determined the oxidative modification of lipoproteins and may play a role in the pathogenesis of atherosclerosis via its protective effect against lipoprotein oxidation in Japanese subjects.

Adult↗
PubMed1996

Hepatitis C virus genotype analysis in patients with type II mixed cryoglobulinemia.

OBJECTIVE: To investigate the possible role of HCV variants in the pathogenesis of mixed cryoglobulinemia. SETTING: Medical service (rheumatology and hepatology units) of urban, university-affiliated teaching hospitals. DESIGN: Analysis of viral genotypes in a cohort of patients with hepatitis C virus (HCV) infection and mixed cryoglobulinemia. PATIENTS: 90 unselected HCV-positive (anti-HCV antibody-positive and HCV RNA-positive) patients consecutively recruited at routine ambulatory visits: 29 with and 61 without (control group) mixed cryoglobulinemia. MEASUREMENTS: Clinical and histologic data; HCV RNA detection in serum and peripheral blood mononuclear cells by polymerase chain reaction (PCR); HCV genotype determination by two methods based on genotype-specific primer PCR and genotype-specific probe hybridization, respectively. RESULTS: Persistent aminotransferase increases were found in 55% of patients with mixed cryoglobulinemia. Peripheral blood mononuclear cells were infected in 80% of cases. In serum samples, HCV genotype 2a/III was detected with a higher prevalence in patients with mixed cryoglobulinemia than in controls (41% compared with 15%). The overall prevalence of genotype 2a/III in mixed cryoglobulinemia increased to 52% when findings in peripheral blood mononuclear cells were also considered. Among patients with mixed cryoglobulinemia, this genotype was more frequent in those without clinical and biochemical signs of liver disease (85%) or with serum autoantibodies (75%). CONCLUSIONS: Mixed cryoglobulinemia may be related, at least in part, to the HCV genotype infecting the host.

Aged↗
PubMed1999

Glutathione S-transferase GSTM3 and GSTP1 genotypes and larynx cancer risk.

Glutathione S-transferases (GSTs) are involved in detoxification of reactive metabolites of carcinogens and, therefore, could be potentially important in susceptibility to cancer. The associations between larynx cancer risk and GSTM3 and GSTP1 gene polymorphisms, either separately or in combination with GSTM1 and GSTT1 gene polymorphisms, were evaluated using peripheral blood DNA from 129 cancer patients and 172 controls, all regular smokers. The frequencies of GSTM3 AA, AB, and BB genotypes were 60.5%, 36.4%, and 3.1% in cases and 72.7%, 24.4%, and 2.9% in controls, respectively. The frequencies of GSTP1 AA, AG, and GG genotypes were 48.1%, 40.3%, and 11.6% in cases and 50.0%, 37.2%, and 12.8% in controls, respectively. Multivariate logistic regression analyses did not reveal any association between the GSTP1 (AG or GG) genotype and larynx cancer [odds ratio, 1.1; 95% confidence interval (CI), 0.7-2.0]. In contrast, a significant increase in risk was related to the GSTM3 (AB or BB) genotype (odds ratio, 2.0; 95% CI, 1.1-3.4). The combined GSTM3 (AB or BB) and GSTM1-null genotype conferred a 4-fold risk (95% CI, 1.6-10.1) of larynx cancer as compared with the combined GSTM3 AA and GSTM1-positive genotype. However, the effect of GSTM3 (AB or BB) genotype was similar among individuals with GSTM1-positive or GSTM1-null genotypes.

Carcinogens↗
PubMed2000

High-activity microsomal epoxide hydrolase genotypes and the risk of oral, pharynx, and larynx cancers.

Human microsomal epoxide hydrolase (mEH), encoded by the EPHX1 gene, is involved in the metabolism of tobacco carcinogens. We investigated the effect of exon 3 and 4 polymorphisms of the EPHX1 gene in 121 patients with cancers of the oral cavity/pharynx, 129 patients with cancer of the larynx, and 172 non-cancer controls, all Caucasian regular smokers. The potential modifying role of previously analyzed GSTM1, GSTM3, and GSTP1 genotypes was also examined. Compared with the putative low-activity genotypes, odds ratios (ORs) associated with predicted intermediate and high mEH activity genotypes were significantly increased for oropharyngeal cancers [OR = 1.8; 95% confidence interval (CI) = 1.0-3.3; and OR = 2.1; 95% CI = 1.0-4.5, respectively; P(trend) = 0.03] and laryngeal cancers (OR = 1.7; 95% CI = 1.0-3.1; and OR = 2.4; 95% CI = 1.1-5.1, respectively; P(trend) = 0.02). Moreover, a positive interaction was found between mEH activity and GSTM3 genotype for laryngeal cancer. The combined EPHX1 high activity-associated genotype and GSTM3 (AB or BB) genotype conferred a 13.1-fold risk (95% CI = 3.5-48.4) compared with the concurrent presence of the EPHX1 low activity-associated genotype and the GSTM3 AA genotype. Thus, EPHX1 polymorphisms may be one of the factors of importance in susceptibility to smoking-related cancers of the upper aerodigestive tract.

Adult↗
PubMed2000

Cigarette smoking, CYP1A1 MspI and GSTM1 genotypes, and colorectal adenomas.

Cigarette smoking has been related to increased risk of colorectal adenomas, but the underlying mechanisms are unknown. Genetic polymorphisms are known for enzymes involved in the activation of polycyclic aromatic hydrocarbons and other tobacco-related carcinogens. Polycyclic aromatic hydrocarbons are activated by cytochrome P4501A1 (CYP1A1) and detoxified by glutathione S-transferases. We investigated the relation of CYP1A1 MspI and GSTM1 genotypes to the risk of colorectal adenomas with special reference to interaction with cigarette smoking among 205 cases of colorectal adenomas and 220 controls with normal total colonoscopy in a male Japanese population. Cigarette smoking was strongly associated with increased risk of colorectal adenomas. Overall, neither the CYP1A1 MspI genotype nor the GSTM1 genotype was related to colorectal adenomas. A significant trend for increased risk of colorectal adenomas associated with smoking was observed for each of the CYP1A1 MspI genotypes, and the increasing trends did not differ by MspI genotype. The positive association between smoking and colorectal adenomas did not vary much with GSTM1 genotypes. Among former and current smokers, adenoma risk did not differ according to the combination of CYP1A1 MspI and GSTM1 genotypes. CYP1A1 MspI and GSTM1 genotypes do not seem to modify the risk of colorectal adenomas associated with cigarette smoking.

Adenoma↗
PubMed2000

Genotypes and phenotypes for apolipoprotein E and Alzheimer disease in the Honolulu-Asia aging study.

BACKGROUND: The utility of apolipoprotein E (ApoE) type as an indicator of genetic susceptibility to Alzheimer disease (AD) depends on the reliability of typing. Although ApoE protein isoform phenotyping is generally assumed equivalent to genotyping from DNA, phenotype-genotype differences have been reported. METHODS: ApoE genotype and phenotype results were examined for 3564 older (ages 71-93 years) Japanese-American male participants of the Honolulu-Asia Aging Study, an ongoing population-based study of aging and dementia. RESULTS: Both methods demonstrated similar associations of ApoE type with AD: a direct association with ApoE4 and a less dramatic inverse association ApoE2. Advanced age did not appear to influence the ApoE4-AD association. The association with AD among ApoE4 homozygotes [odds ratio (OR) = 14.7] was higher than expected based on an observed OR of 2.0 in heterozygotes. Phenotype-genotype nonconcordance was more frequent for ApoE2 than for ApoE4. The ApoE2 phenotype occurred at a frequency of 7.9% vs a genotype frequency of 4.9%, corresponding to a probability of 56% that an individual with ApoE2 phenotype had the same genotype. CONCLUSIONS: Whereas E4 and E2 phenotypes and genotypes were comparably associated with AD, neither method would be expected to substantially improve the efficiency of case finding in the context of population screening beyond prediction based on age and education. Nonconcordance of phenotype and genotype was substantial for E2 and modest for E4 in this population. The ApoE4-AD association was independent of age.

Aged↗
PubMedDate not supplied

Distribution of hepatitis C virus genotypes in patients with chronic hepatitis C in northern Estonia.

Distribution of hepatitis C virus (HCV) genotypes among 30 patients with chronic liver diseases and antibodies to HCV (anti-HCV) was investigated. Sera of these patients were analyzed for HCV genotype by reverse transcription-polymerase chain reaction (RT-PCR) and restriction fragment length polymorphism (RFLP) analysis of the 5'-non-coding region (5'-NCR) of the virus genome and for HCV serotype by detecting antibodies to HCV NS4 peptides by enzyme-linked immunosorbent assay (ELISA). The following distribution of genotypes was found: genotypes 1b in 32.0%, 3a in 20.0%, 2a in 12.0% and 1a/b (double infection) in 28.0%. The results of serotyping were interpretable in 92.0% and concordant with those of genotyping in 80.0% of the patients. In Northern Estonia, the genotypes 1b and 3a seem to be most common in chronically infected patients. Serotyping is an generally available and cheap assay and can be performed in most diagnostic laboratories in comparison to genotyping. However, genotyping is a more sensitive and more specific assay.

5' Untranslated Regions↗
PubMed2001

[A method of genotyping clinical isolates of Ureaplasma urealyticum biovar Parvo].

A new method for typing clinical isolates of U. urealyticum (Parvo biovar) is based on SSCP analysis of amplicons of mba gene 5' region and upstream region. The mba gene is coding for MB gene of U. urealyticum. This method allows genotyping of U. urealyticum isolates using vaginal and cervical swabs without culturing. Sixty-two clinical specimens from patients with a history of chronic cystitis, chronic pyelonephritis, chronic salpingo-oophoritis, erosion of the cervix uteri, and spontaneous abortions were tested for U. urealyticum. The bacterium was detected in 64% (40 specimens), 83% (33) of which belonged to Parvo biovar. Parvo biovar isolates were analyzed and genotyped as follows: first genotype 52%, second genotype 33%, and third genotype 16%. Further sequencing of the first and second genotype amplicons showed that the first genotype belonged to serotype 3 and second genotype to serotype 6.

Amino Acid Sequence↗
PubMed2001

Effect of mercury and Gpi-2 genotype on standard metabolic rate of eastern mosquitofish (Gambusia holbrooki).

Previous studies demonstrated differential mortality among mosquitofish of different Gpi-2 genotypes during acute mercury and arsenate exposures. Mercury-exposed mosquitofish also had Gpi-2 genotype-specific differences in glycolytic and Krebs cycle metabolite pools. The mortality and metabolite data suggested that mosquitofish bearing specific Gpi-2 genotypes might differ in metabolic efficiency, with less efficient Gpi-2 genotypes having higher standard metabolic rates (SMRs) and shorter times to death during acute mercury exposure. Effect of Gpi-2 genotype on SMR was assessed with a factorial arrangement of six Gpi-2 genotypes and two exposure sequences (Control - Control; Control - 100 microg/L Hg). The SMRs were estimated by measuring oxygen consumption using an indirect, closed-circuit, computer-controlled respirometer. A 48-h exposure to 100 microg/L of mercury resulted in a 16.7% elevation of SMR above control levels (p = 0.001). The Gpi-2 genotype and the number of heterozygous loci per individual had no significant effect on SMR in mercury-exposed mosquitofish. The experimental results do not support the hypothesis that Gpi-2 genotype-specific differences in glycolytic and Krebs cycle metabolite pools and mortality in mosquitofish exposed to mercury are associated with differences in SMR.

Animals↗
PubMed2000

[Distribution of TT virus genotypes in blood donors of northern China].

OBJECTIVE: To analyse the distribution of TT virus (TTV) genotypes in the blood donors of Northern China. METHODS: TTV DNA was detected using nested-PCR and its PCR products were cloned into the pGEM-T vector for sequencing. The sequences were analysed using ClustalX and Neighbor joining programs. RESULTS: Nucleotide identity of the 12 strains of Chinese TTV isolated was 53%-95%. Nucleotide homology between the representatives of genotype 1a and 1b [TX011(O), TA278] and the 12 strains of TTV was 55%-94% and 55%-75%, respectively. Of the 12 Chinese TTV isolates, eight were classified as genotype 1b, three as unknown genotype X and one as unknown genotype Y, which accounted for 66.7%, 25% and 8.3%, respectively. CONCLUSIONS: An exceptional degree of genetic heterogeneity was displayed in TTV nucleotide sequences and they could be, at least, classified as three genotypes. Genotype 1b may be the main prevalent genotype in blood donors of Northern China.

Amino Acid Sequence↗
PubMed2001

Genotypic differences in the presence of hairs on roots and gynophores of peanuts (Arachis hypogaea L.) and their significance for phosphorus uptake.

Root hairs substantially increase the surface area of plant roots with positive effects for phosphorus (P) uptake, but the ability of peanuts to form root hairs has been questioned. The aim was to examine hair development on roots and gynophores of a variety of peanut genotypes and to relate genotypic differences in hair formation to differences in P uptake. Five out of eighteen genotypes completely lacked hairs on both organs whereas others consistently developed hairs on roots and gynophores, although with considerable variation in hair density. The ability to form root hairs as well as root hair density concurred with the presence and density of hairs on gynophores, suggesting a possible connection between both developmental processes. The contribution of root hairs to P uptake was studied in three genotypes differing in hair density. The final amount of P taken up by roots did not differ between genotypes but two distinct P uptake strategies could be identified. The genotype lacking root hairs maintained P uptake due to the development of a large root system whereas densely covered roots of genotype 'Wasedairyu' were three times as efficient in extracting P from a P-deficient soil. Furthermore P uptake through gynophores contributed about 20% to the total P uptake of Wasedairyu but only insignificant amounts to other genotypes. The ability to form hairs on roots and gynophores can therefore be seen as an adaptation to low P availability and if combined with a large root system, could substantially increase the tolerance of peanuts to P deficiency.

Arachis↗
PubMed2001

Phylogenetic analysis of new hepatitis B virus isolates from Nigeria supports endemicity of genotype E in West Africa.

Isolates of hepatitis B viruses were collected from 20 acute and chronic hepatitis patients in a highly endemic region of Nigeria. Sequencing classified the isolates to the ayw4, as they all contained the amino acid variations characteristic for that serotype. In the pre-S2 region of five isolates, three to seven amino acids were deleted, suggesting that immune escape mutations previously associated only with chronic HBV infection may be observed also in acute disease. Phylogenetic analysis of the complete pre-S2/S (large S) genes (831 nt) demonstrated that all the viruses belonged to the same genotype E. So far, no isolates of genotype E have been found in any other region of the world, including the Americas. This may suggest a relatively recent introduction of this genotype into humans and would explain the relatively low genetic diversity of viruses belonging to this genotype. One genotype E virus had been found previously in a chimpanzee, and viruses belonging to the CHIMP genotype are related to other genotype E viruses. These findings are compatible with a transmission of genotype E viruses from chimpanzees to humans.

Amino Acid Sequence↗
PubMed1999

[Relationship between glutathione S-transferase M1, T1 genotype and susceptibility to gastric cancer].

OBJECTIVE: The objective of this study was to examine the association between glutathione s-transferase M1, T1 genotype and the risk of gastric cancer. METHODS: A case-control study was carried out and polymerase chain reaction (PCR) technique was used to identify GST M1, GST T1 genotype in 95 cases of primary gastric cancer and 94 controls. RESULTS: The frequency of GST M1 null genotype was 63.16% and 45.74%, respectively in gastric cancer cases and control group, with statistically significant difference (chi(2) = 5.75, P = 0.0165). GST M1 null genotype correlated with the susceptibility to gastric cancer (OR = 2.03, 95% CI of OR = 1.09 - 3.80). The risk for gastric cancer in those with GST M1 null and GST T1 non-null genotype was significantly higher than that in those with GST M1 non-null and GST T1 null genotype, with an OR of 2.91 and 95% CI of ORs 1.09 - 7.89. The risk for gastric cancer in those smoking with GST M1 null genotype increased significantly (OR = 8.06, 95% CI of OR = 2.83 - 23.67). CONCLUSION: GST M1 null genotype was associated with the risk for gastric cancer.

Adult↗
PubMed2002

Prevalence of interleukin 1 periodontal genotype in a Hispanic dental population.

OBJECTIVE: A genetic polymorphism in the interleukin 1 gene has been implicated as a factor in determining the severity of adult periodontitis. Among white Europeans, the prevalence of genotype-positive subjects has been reported to be around 30%. The purpose of this study was to assess the prevalence of genotype-positive individuals in a Hispanic population. METHOD AND MATERIALS: Fifty Mexicans were evaluated for their interleukin 1 genotype with a commercially available test. Subjects were divided into groups, as determined by their genotype (positive or negative), and were then analyzed according to age, sex, and smoking habits. RESULTS: Thirteen of 50 subjects were genotype positive, a prevalence of 26%. The most common polymorphisms found in genotype-positive subjects were allele 1.2 for the IL 1A gene and allele 1.2 for the IL 1B gene. When only subjects older than 30 years were evaluated, the prevalence of genotype-positive individuals was 31%. CONCLUSION: The prevalence of genotype-positive subjects in a Hispanic population was 26%, similar to the prevalence found among ethnic populations from or descended from Northern, Central, and Southern Europe.

Adolescent↗
PubMed2002

[Identification and genotyping of Norwalk virus by stringent microplate hybridization of PCR products].

There are many genotypes of Norwalk virus(NV), and the microplate hybridization method for identification and genotyping of NV requires preparation of many probes. However, the method is simple and the detection sensitivity is high at 10 ng/ml DNA, and many samples can be simultaneously examined in an identification test and genotyping of NV. Increasing the hybridization temperature increases precision and the homology rate between a probe and DNA fragment can be estimated. Mixed genotypes of NV are often detected in a same sample of NV-infected patients and oysters. In such cases, genotypes cannot be determined by direct sequencing. However, this method is applicable to genotyping of cases infected with mixed genotypes. Genotypes can be determined without sequencing by preparing many probes.

Genotype↗