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PubMedDate not supplied

HCV genotypes and cryoglobulinemia.

OBJECTIVE: To evaluate the HCV genotype distribution in subjects affected by cryoglobulinemia in order to verify its possible role in the pathogenesis of the disease and to provide the clinician with a useful datum for therapy. METHODS: Nested PCR with universal and type-specific primers was used for the genotyping. RESULTS: Genotype I (1a) was never present in cryoglobulinemia, while it was present in 7 (4.3%) patients with chronic hepatopathy and in 4 (10.8%) asymptomatic patients. Type II (1b) was present in 28 (58.3%) and in 8 (47.1%) cryoglobulinemic patients with and without hepatopathy, respectively, in 106 (64.6%) patients with chronic hepatitis; in one patient with acute hepatitis; and in 14 (37.9%) asymptomatic patients. Type III (2a) was present in 2 (4.2%) and 2 (11.8%) cryoglobulinemic patients with and without hepatopathy, respectively; in 1 (0.6%) patient with chronic hepatopathy; and in 2 (5.4%) asymptomatic subjects. Type IV (2b) was present in 1 (2.1%) and in 2 (11.8%) cryoglobulinemic patients with and without hepatopathy, respectively; in 5 (3%) patients with chronic hepatopathy; and in 1 (2.7%) asymptomatic subject. Coinfections were present in 42 cases: 6 (12.5%) cryoglobulinemia with hepatopathy, 4 (23.5%) cryoglobulinemia without hepatopathy, 25 (15.3%) chronic hepatopathy, and in 7 (18.9%) asymptomatic subjects. For 41 (15.4%) strains typing was not possible. Eight of the "untypable" strains and 3 strains from patients with coinfection proved to belong to a new genotype. CONCLUSIONS: Genotype II (1b) was the most frequent in patients with and without cryoglobulinemia; genotype I (1a) was absent in all 65 patients with cryoglobulinemia, in whom, however, as in the subjects without cryoglobulinemia, all the other genotypes could be found. An interferon-resistant genotype characterized by an elevated homology with Simmonds' type 2c (rare genotype) was present.

Cryoglobulinemia↗
PubMed1996

Serotypes, genotypes and levels of hepatitis C viremia in pregnant women in Taiwan.

The correlation between a new serotyping method for grouping different genotypes of hepatitis C virus (HCV) and those identified by a polymerase chain reaction (PCR) assay with type-specific primers was investigated in 3,400 pregnant women. The correlation between HCV genotypes and serum HCV levels in HCV-positive pregnant women was studied as well. The new serologic assay used an enzyme-linked immunosorbent assay (ELISA) based on highly group-specific recombinant peptides (C14-1 and C14-2) within the NS4 region and detected group-specific antibodies against different HCV genotypes. Serum HCV levels were assayed by a competitive PCR method. In all, 43 pregnant women were found to be positive for HCV antibodies by the second-generation ELISA method and were positive for HCV-RNA by PCR with primers from the 5' untranslated region. All 43 had defined genotypes: 28 (65%) with HCV 1b, 11 (26%) HCV 2a, 3 (7%) HCV 2b and 1 (2%) HCV 1b + 2a. In 40 (93%) of the 43 viremic pregnant women, the results of serotyping by ELISA showed complete agreement with those determined by PCR genotyping, and none of the women showed a group different from that of the HCV genotype. In addition, serum levels of HCV 1b were significantly higher than those of HCV 2a. The results show that this new serotyping assay is highly sensitive and specific for the determination of HCV genotypes and that serum HCV levels in pregnant women with genotype 1b are higher than those with genotype 2a.

DNA, Viral↗
PubMed1996

Increased risk of hepatocellular carcinoma in patients infected with hepatitis C genotype 1b.

UNLABELLED: Infection with hepatitis C virus (HCV) genotype 1b has been reported to be associated with more severe liver disease and an unfavorable outcome. Liver transplantation allows for a complete examination of the explanted liver for the detection of hepatocellular carcinoma (HCC). OBJECTIVE: To study the prevalence of HCC in patients with liver cirrhosis secondary to chronic infection with HCV genotype 1b compared with those infected with other genotypes. METHODS: Sera were collected from 48 consecutive patients undergoing liver transplantation for end stage liver disease secondary to HCV infection. RNA was extracted from serum using chaotropic lysis and isopropanol precipitation. Reverse transcriptase-polymerase chain reaction of the NS5 region was performed, followed by automated sequencing on desalted amplification products. Genotype assignment followed Simmonds's classification. All explanted livers were examined for the presence of HCC. RESULTS: HCV genotypes in our patients were as follows: subtype 1a, 20 patients (42%); 1b, 18 patients (37.5%); 2a, one patient (2%); 2b, six patients (12.5%); 3a, one patient (2%); and 4a, two patients (4%). Although five of 18 patients infected with HCV genotype 1b (28%) had HCC, only one of 30 patients (3%) infected with all other genotypes (1a, 2a, 2b, 3a, and 4a) had HCC (p = 0.02). CONCLUSION: Infection with HCV genotype 1b may carry a higher risk for the development of HCC than infection with other HCV genotypes.

Adult↗
PubMed1996

[Prevalence of the genotypes of the hepatitis C virus in Spanish drug addicts with chronic hepatitis C. Spanish Group for the Study of Viral Hepatitis in HIV Positive Patients].

The hepatitis C virus (HCV) shows a wide genetic variability. The different variants of HCV have been classified into 9 types and different subtypes. Some genotypes have a characteristic geographic distribution and seem to be associated with precise ways of contagion. Serum samples from 107 spanish patients with chronic hepatitis C were studied, which were distributed as follows: 88 parenteral drug addicts (PDA) and a control group of 19 subjects made up by 4 transfused, 5 probably sexually infected and 10 with unknown contagion source (sporadic cases). HCV typing was made by means of the PCR method and later hybridization analysis with complementary probes of different types and subtypes of HCV exposed on a smooth surface (Inno-LiPA). A total to 105 (98.4%) patients had their viruses genotypes. There was more than one genotype in the same subject (co-infection) in 43.8% of cases and co-infection 1a + 1b was the most common (82.7%). While not reaching a statistic significance, co-infections were more frequent in PDA (47.1%) than in the remaining patients (27.8%). In the infected patients with only one genotype, the most common genotype was 1a, both in PDA (22.9%) and in subjects with transfusional HCV, sexual or sporadic (38.9%). In decreasing frequency came genotypes 1b (13.3%) and 3a (11.4%). Other genotypes were very uncommon (2a and 4) or were absent (2b and 5) as unique infections. In conclusion, genotypes non-1b of HCV, mainly 1a and to a lesser extent 3a, are the most common in a spanish population made up mainly by young persons with risk antecedents for HIV infection, particularly PDA. Furthermore, co-infection with HCV genotypes is frequent in this population.

Adult↗
PubMedDate not supplied

Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium.

OBJECTIVE: To examine more closely the association between apolipoprotein E (APOE) genotype and Alzheimer disease (AD) by age and sex in populations of various ethnic and racial denominations. DATA SOURCES: Forty research teams contributed data on APOE genotype, sex, age at disease onset, and ethnic background for 5930 patients who met criteria for probable or definite AD and 8607 controls without dementia who were recruited from clinical, community, and brain bank sources. MAIN OUTCOME MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for AD, adjusted for age and study and stratified by major ethnic group (Caucasian, African American, Hispanic, and Japanese) and source, were computed for APOE genotypes epsilon2/epsilon2, epsilon2/epsilon3, epsilon2/epsilon4, epsilon3/epsilon4, and epsilon4/epsilon4 relative to the epsilon3/epsilon3 group. The influence of age and sex on the OR for each genotype was assessed using logistic regression procedures. RESULTS: Among Caucasian subjects from clinic- or autopsy-based studies, the risk of AD was significantly increased for people with genotypes epsilon2/epsilon4 (OR=2.6, 95% CI=1.6-4.0), epsilon3/epsilon4 (OR=3.2, 95% CI=2.8-3.8), and epsilon4/epsilon4 (OR=14.9, 95% CI= 10.8-20.6); whereas, the ORs were decreased for people with genotypes epsilon2/epsilon2 (OR=0.6, 95% CI=0.2-2.0) and epsilon2/epsilon3 (OR=0.6, 95% CI=0.5-0.8). The APOE epsilon4-AD association was weaker among African Americans and Hispanics, but there was significant heterogeneity in ORs among studies of African Americans (P<.03). The APOE epsilon4-AD association in Japanese subjects was stronger than in Caucasian subjects (epsilon3/epsilon4: OR=5.6, 95% CI=3.9-8.0; epsilon4/epsilon4: OR=33.1, 95% CI=13.6-80.5). The epsilon2/epsilon3 genotype appears equally protective across ethnic groups. We also found that among Caucasians, APOE genotype distributions are similar in groups of patients with AD whose diagnoses were determined clinically or by autopsy. In addition, we found that the APOE epsilon4 effect is evident at all ages between 40 and 90 years but diminishes after age 70 years and that the risk of AD associated with a given genotype varies with sex. CONCLUSIONS: The APOE epsilon4 allele represents a major risk factor for AD in all ethnic groups studied, across all ages between 40 and 90 years, and in both men and women. The association between APOE epsilon4 and AD in African Americans requires clarification, and the attenuated effect of APOE epsilon4 in Hispanics should be investigated further.

Adult↗
PubMed1998

Association of glutathione S-transferase GSTM1 and GSTT1 null genotypes with clinical outcome in epithelial ovarian cancer.

Epithelial ovarian cancer is generally associated with a poor outcome, although the mechanisms that determine survival and progression-free interval (PFI) are unclear. Data from ovarian tumors showing associations between (a) null genotypes at the glutathione S-transferase GSTM1 and GSTT1 loci and expression of p53 protein and (b) outcome and expression of p53 suggest that polymorphism at these loci is a factor determining outcome. Accordingly, we have studied the association between the GSTM1 null and GSTT1 null genotypes and survival and PFI in 148 women with epithelial ovarian cancer. Although we did not find an association between individual genotypes and outcome, women with both GSTM1 null and GSTT1 null genotypes demonstrated poorer survival (P = 0.001) and reduced PFI (P = 0.003). Thus, no cases with both these genotypes survived past 42 months postdiagnosis. In contrast, 43% of the women without this combination survived beyond this time. Because response to chemotherapy is a major factor determining outcome in ovarian cancer, we also examined the data for associations between the glutathione S-transferase genotypes and response to such treatment. Thus, in 78 patients treated with chemotherapy, the combination of GSTM1 null and GSTT1 null was associated with unresponsiveness to primary chemotherapy (P = 0.004); none of the eight patients with both these genotypes responded, compared with 38 of 70 (54%) of patients with other genotype combinations. The effect of the combination of genotypes on survival and PFI was lost in a multivariate model that included response to chemotherapy as a confounding factor. This suggests that the combination of GSTM1 null/GSTT1 null is associated with outcome because of its influence on response to chemotherapy. These preliminary findings may provide a basis for the selection of patients for treatment with chemotherapeutic agents.

Adolescent↗
PubMed1999

Mixed genotypes infection with hepatitis D virus.

Heterogeneity of hepatitis C viral (HCV) genomes results in escape from immune clearance. Super-infection or mixed infection of different genotypes of HCV are seen commonly in humans. Hepatitis D virus (HDV) is classified into 3 genotypes. This study was planned to investigate if mixed genotypes infection of HDV occurs in humans. HDV genotyping based on restriction fragment length polymorphism (RFLP) was used to screen 60-99 HDV clones from each case of 7 prostitutes and 11 patients. Mixed infections were diagnosed by the finding of two or more different RFLP patterns in a case and were confirmed by sequencing. Five prostitutes had mixed infections of genotypes IIa and IIb HDV, while only 2 patients had mixed infections of genotypes I and II HDV (P< 0.05). The heterogeneity in nucleotide sequence was generally below 2% among HDV quasi-species from the same subject, while the heterogeneity was 27.7% between genotypes I and II HDV, and 22.8% between genotypes IIa and IIb HDV from a subject with mixed infection. Multiple HDV clones from the spouses of the 2 index cases were also analyzed. One spouse had mixed infection and the other did not, corresponding to the index cases. In cases with mixed genotypes infections, the prevalence of the minor strain was less than 10% of the total colony population analyzed.

Adult↗
PubMed2026

Scalable medium-density genotyping platforms for cultivar identification, pedigree authentication, marker-assisted and genomic selection, and other applications in strawberry.

A broad spectrum of high-density genotyping approaches, including single-nucleotide polymorphism (SNP) arrays, genotyping-by-sequencing, and whole-genome reduced-representation sequencing, have been shown to perform well in strawberry (Fragaria &#xd7; ananassa), despite the inherent complexity of the octoploid genome. While these approaches are effective, their routine deployment in breeding programs can be constrained by cost, computational requirements, and workflow complexity. In parallel, many breeding programs continue to rely on locus-specific assays for marker-assisted selection, resulting in fragmented and inefficient genotyping strategies. Here, we describe medium-density amplicon-based genotyping platforms for strawberry designed to provide cost-effective, turnkey solutions that integrate markers used for marker-assisted selection with genome-wide markers suitable for genomic prediction in a single laboratory assay. These platforms were developed by targeting 1,650 or 4,811 target SNPs via amplicon sequencing, and are interoperable with existing high-density genotyping resources, including a widely used 50K SNP array, thereby facilitating data integration across platforms. We benchmarked their performance relative to the 50K SNP array across breeding-relevant applications, including identity and purity testing, pedigree authentication, marker-assisted selection, and genomic selection, and further evaluated the feasibility of genotype imputation to enhance genome-wide information content. Across analyses, the 1,650- and 4,811-amplicon platforms produced results comparable to higher-density platforms while substantially reducing genotyping cost and analytical overhead. This work demonstrates that targeted amplicon-based genotyping can support efficient, scalable, and integrated genome-informed breeding, enabling the routine application of both marker-assisted and genomic selection within strawberry breeding workflows. Open-source R workflows are provided to support streamlined analyses in breeding contexts.

Fragaria↗
PubMed1997

Hepatitis C virus genotypes in French haemophiliacs: kinetics and reappraisal of mixed infections.

The distribution and kinetics of hepatitis C virus (HCV) genotypes and the prevalence of mixed infections were studied in a group of 45 French patients with haemophilia A or B or von Willebrand's disease, 21 of them being anti-human immunodeficiency virus (HIV) positive; genotyping was carried out by three methods based on the core, 5' untranslated region (5'UTR), and the detection of type-specific NS4 antibodies. Genotyping of the 5'UTR revealed genotypes 1a (n = 10), 1b (n = 13), 2a (n = 3), 2b (n = 4), 2NC (n = 3), 3a (n = 10), and two mixed infections (1a + 1b and 3a + 2). Five of 33 patients showed a change from one HCV genotype to another. The core genotyping assay showed 8 of 45 mixed infections: 6/8 1a + 1b and 2/8 3a + 2. Sequencing of core polymerase chain reaction (PCR) products showed that mixed infection 1a + 1b could be explained by nonspecific annealing of the 1b primer to type 1a sequence. By designing new primers whose sequence was more specific to HCV types 1a and 1b, we could confirm 1a + 1b mixed infection in only one of six cases. Serotyping assay showed for 17 of 21 anti-HIV negative patients a concordance with the 5'UTR genotype; however, only 6 of 19 anti-HIV positive patients showed detectable serological reactivity. In summary, we have observed a similar HCV genotype distribution between our haemophilic group and the French anti-HCV positive patients. The study demonstrates the difficulties of assessing with the presently available genotyping and serotyping assays the real prevalence of mixed infections in multiply transfused patients.

Antigens, Viral↗
PubMed2002

Relation between angiotensin-converting enzyme II genotype and atrial fibrillation in Japanese patients with hypertrophic cardiomyopathy.

Atrial fibrillation (AF) occurs in about 20% of patients with hypertrophic cardiomyopathy (HCM). HCM patients with AF have an increased risk for clinical decline and thromboembolism. In addition, AF is known to be associated with the atrial renin-angiotensin system (RAS). However, the relation between AF and the RAS in HCM has not been investigated. We genotyped the insertion/ deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in 138 HCM patients (26 with AF, 112 with sinus rhythm). Distribution of the ACE genotypes (DD, ID, and II) among the total HCM patients was 15%, 46%, and 38%. AF was documented in 3 patients with the DD genotype, 7 with the ID genotype, and 16 with the II genotype (P < 0.03 vs. sinus rhythm group). The odds of AF were 3.2-fold greater in patients with the II genotype than in those with the other genotypes (P = 0.009, 95% confidence interval = 1.3-7.8). Kaplan-Meier curves examining the time to the first documented AF event showed a significant difference between genotypes during the follow-up period (mean 116 months, P < 0.05). These findings suggest that the II genotype of the ACE gene is a significant risk factor for AF in patients with HCM.

Aged↗
PubMed2006

Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan.

In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a difference in clinical features between the two genotypes remains unclear. This study compares the clinical features of patients infected with the two. From January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients with genotype 4 were enrolled. Patients with genotype 4 had significantly higher peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747-4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series, patients with genotype 4 had longer median duration of hospital stay (26.5 days, 18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection tended to have more severe clinical manifestations than those with genotype 3 infection.

Journal Article↗
PubMed2000

The behavioural, physiological and immunological responses of lambs from two rearing systems and two genotypes to exposure to humans.

The behavioural, physiological and immunological responses of lambs from two rearing systems and two genotypes to exposure to humans was assessed during and immediately after testing in an open-field arena. Ninety-six lambs of two genotypes (Scottish Blackface: BF and Texelx(Blue-faced LeicesterxScottish Blackface): T) were used. From birth to weaning one of two management regimes was applied: extensive (E), whereby animals were handled as little as possible or semi-intensive (I), in which lambs experienced a greater level of human exposure. Eight lambs from each of the four treatment groups received an antigenic challenge (Mycobacterium a. paratuberculosis) at 9 weeks of age to allow subsequent testing of immunological reactivity. At 1 and 3 weeks after weaning and 1 year later, lambs were tested in groups of four in a 4.5x4.5 m indoor arena, marked with gridlines at 0.75 m intervals. There were a number of occasions where testing revealed significant effects of genotype, management or their interaction, but in an approximately equal number of instances no significant effects of either genotype or management were observed. Genotype significantly influenced the number of squares occupied in the test arena over a 10-min period before the human entered (100.4 vs. 110.5; sed 2.70 for BF and T lambs, respectively, p<0.001). In relation to the number of new squares entered, there was a genotypexmanagement interaction: BFE lambs entered fewer squares than TE lambs but following semi-intensive management (I) BF lambs entered more squares than T lambs (p<0.05). When a human entered the arena after this 10-min period, while there was a gradual reduction in the number of animals which had not moved over the next 5 min, 66 animals had not moved within the allocated time. Also during this period, BF lambs stood facing the human for significantly longer than T lambs (p<0.05). At the time of arena testing, 12 lambs from each treatment group were fitted with heart-rate monitoring equipment. There were significant differences in heart rate in relation to period of testing, i.e. before (107.9) or after (112.3) the point at which the human entered the arena or when the lambs were walking in the presence of a moving human (126.3 b.p.m.; sed 2.15, p<0.001). When lambs were alone in the test arena, BF lambs had higher heart rates than T lambs (p<0.05). The heart rate of E lambs increased more than that of I lambs when the human entered the pen (9.4 vs. 0.3 b.p.m.; sed 3.95, respectively; p=0.05). Immediately following completion of the behavioural tests, blood samples were collected from subsets of lambs. Plasma cortisol concentrations of BF lambs were greater than those of T lambs (82.0 vs. 53.5 nmol/l; sed 10.18, p<0.01) but there was no effect of management. Blood samples collected from the lambs challenged with a novel antigen prior to weaning showed a genotype but not a management effect on both antibody and cell mediated immune responses, although there was a genotypexmanagement interaction. However, it should also be noted that there were no significant effects of either genotype or management on a number of the indices recorded: latency of lambs to move from the initial entry position in the absence or subsequent presence of a human; length of time one individual was separated from the other three; distance moved in a raceway before stopping; plasma beta-endorphin concentrations; heart rate in the presence of a human. Overall, these results suggest that although differences in responsiveness associated with specific genotypes of sheep can be detected in a test situation, the early life management regime may also have an effect. The results of this study caution against drawing conclusions between studies where different genotypes are employed.

Journal Article↗
PubMed2001

Relation of collagen type I alpha 1 (COLIA 1) and vitamin D receptor genotypes to bone mass, turnover, and fractures in early postmenopausal women and to hip fractures in elderly people.

Background: In a previous study, we showed an association between the vitamin D receptor (VDR) gene BsmI restriction fragment polymorphism and peak bone mass in young Finnish adults. Design: The previous finding prompted us to study the relationship of the same polymorphism, as well as of the polymorphism in the Sp1 binding site of the collagen type I alpha 1 (COLIA 1) gene, to bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry and adjusted for age, weight, height, and lifestyle factors. Also studied was the relationship of VDR and COLIA 1 genotypes to markers of bone turnover [serum osteocalcin, type I procollagen carboxy- (PICP), and aminoterminal (PINP) propeptide, and type I collagen carboxyterminal telopeptide (ICTP)] and bone fractures in 513 early postmenopausal women (1-5 years postmenopausal), as well as hip fractures in 172 very old people. Results: The BB, Bb, and bb genotypes of the VDR gene, as well as the SS, Ss, and ss genotypes of the COLIA 1 gene, were distributed similarly among 402 early postmenopausal women with osteopenia in the lumbar spine and among 111 women with normal BMD (P=0.12 for VDR, P=0.53 for COLIA 1). There was no relation between the VDR and COLIA 1 genotypes and lumbar spine BMD among osteopenic women, among normal women, or in the combined study population. Among the women with vertebral osteopenia, the femoral neck BMD did not associate significantly with the VDR or COLIA 1 polymorphisms. The frequencies of the different VDR and COLIA 1 genotypes were similar among women with or without a history of a low-energy fracture. There was a borderline association between the VDR genotype and serum osteocalcin concentrations, with the Bb genotype associated with the highest median level (P=0.037). In a population-based sample of very old individuals (>85 years), the frequencies of the different VDR and COLIA 1 genotypes were similar among those with (n=64) and without (n=108) a history of hip fracture. Conclusion: The present data suggest that, in the Finnish population, the VDR and COLIA 1 genotypes do not determine the bone mass of early postmenopausal women or their bone turnover rate. The polymorphisms are not associated with risk of hip fractures in elderly people or with low-energy fractures in early postmenopausal women.

Journal Article↗
PubMed2002

Cytomegalovirus glycoprotein B genotype does not correlate with outcomes in liver transplant patients.

BACKGROUND: Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested there could be an association between CMV gB genotype and clinical outcome in transplant patients. OBJECTIVES: The goal of this study was to determine the distribution of gB genotypes in a cohort of liver transplant recipients with CMV infection and the effect of gB type on clinical outcomes including CMV disease and rejection. STUDY DESIGN: DNA was extracted directly from the blood of 58 liver transplant recipients with CMV infection. The gB genotype of CMV was determined using the polymerase chain reaction to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Results were correlated with CMV viral load, symptomatic disease, and development of acute rejection. RESULTS: The distribution of CMV gB genotypes was: gB1, 15/58 (25.9%); gB2, 16/58 (27.6%); gB3, 21/58 (36.2%); gB4, 2/58 (3.4%) and four patients (6.9%) had mixed infection. No correlation between CMV genotype and peak CMV viral load was observed. Symptomatic CMV disease developed in 25/58 (43.1%) patients and 26/58 (44.8%) had acute rejection. The rate of CMV disease and acute graft rejection in patients infected with the different CMV gB genotypes was not significantly different. However, all four patients with infection with a mixture of CMV gB genotypes developed progression to CMV disease (P=0.030). CONCLUSIONS: The gB genotype did not correlate with peak CMV viral load and with the development of CMV disease or acute rejection following liver transplantation.

Acute Disease↗
PubMed2006

Genotyping of human cystic echinococcosis in Xinjiang, PR China.

The Xinjiang Uygur Autonomous Region, multi-ethnic province in northwestern China, is one of the most important foci of human cystic echinococcosis (CE) in the world. Two Echinococcus granulosus genotypes (G1 and G6) are known to infect the intermediate hosts in this area but, to date, the source of the human infection remains unclear. The current study aimed to genetically analyse 67 hydatid cysts removed from 47 CE patients for which epidemiological, clinical and serological data were also recorded. Mitochondrial cox 1 gene sequencing suggested that the E. granulosus G1 genotype is the major source of infection (45/47 CE patients). Nevertheless, for the first time in China, 2 patients were found with hydatid cysts of the G6 genotype. In addition, 45 E. granulosus gravid tapeworms, isolated from 13 dogs, were genotyped. The majority of adult worms (42/45) exhibited the G1 genotype, whereas 3 adult tapeworms with the G6 genotype were found in one dog, that also harboured E. granulosus tapeworms of the G1 genotype. This sympatric occurrence of G1 and G6 genotypes of E. granulosus, not only in the same area but also in the same definitive host, raises the interesting question of putative genetic recombination between these E. granulosus genotypes.

Adolescent↗
PubMed1998

Relationship of vacA genotypes of Helicobacter pylori to cagA status, cytotoxin production, and clinical outcome.

BACKGROUND: Mosaicism in vacA alleles with three distinct families of vacA signal sequences (s1a, s1b and s2) and two distinct families of middle region alleles (m1 and m2) has been reported. It was suggested that the vacA s1a genotype was closely associated with duodenal ulcer disease and with high cytotoxin production. The aim of this study was to evaluate the role of vacA genotyping with respect to gastric inflammation and injury, cytotoxin activity, and clinical presentation. METHODS: H. pylori from patients with gastritis, peptic ulcer disease, or gastric cancer were characterized by vacA typing by polymerase chain reaction (PCR) and DNA sequencing. In vitro cytotoxin activity was assessed by vacuolation assay using Vero cells as well as with Hela cells. RESULTS: Four hundred ninety-one strains were tested. vacA genotype s1a/m1 was present in more than 95% of strains independent of presentation with gastritis, peptic ulcer, or gastric cancer. No vacA genotype was associated with high average cytotoxin activity. The s2/m2 isolates had low or absent cytotoxin activity. All cagA negative strains (n = 18) were s1a strains and both s2/m2 strains were cagA positive. One strain that was a recombinant of m1 and m2 strains was identified and had low cytotoxin activity. The nucleotide and amino acid sequences between original m1 strains and Japanese m1 strains (new m1 strains) were about 85% and 81%, respectively. Strains with the new m1 genotype had nucleotide and amino acid sequences similarity of more than 96%. There was no difference in cytotoxin activity between strains with the Western type m1 and the new type m1 genotype. CONCLUSION: In this as in other reported studies ( approximately 1500 patients overall) vacA genotype was strongly but not exclusively associated with the presence of cagA. Overall, the studies did not support a role for vacA genotyping in relation to cytotoxin activity, virulence, histologic finding, or risk of a particular H. pylori disease. vacA genotype s1 is likely to be a surrogate marker for the presence of the cag pathogenicity island.

Adult↗
PubMedDate not supplied

Contribution of different HFE genotypes to iron overload disease: a pooled analysis.

PURPOSE: To determine the contribution of the C282Y and H63D mutations in the HFE gene to clinical expression of hereditary hemochromatosis. METHODS: Pooled analysis of 14 case-control studies reporting HFE genotype data, to evaluate the association of different HFE genotypes with iron overload. In addition, we used data from the pooled analysis and published data to estimate the penetrance of the C282Y/C282Y genotype. RESULTS: Homozygosity for the C282Y mutation carried the largest risk for iron overload (OR = 4383, 95% CI 1374 to >10,000) and accounted for the majority of hemochromatosis cases (attributable fraction (AF) = 0.73). Risks for other genotypes were much smaller: OR = 32 for genotype C282Y/H63D (95% CI 18.5 to 55.4, AF = 0.06); OR = 5.7 for H63D/H63D (95% CI 3.2 to 10.1, AF = 0.01); OR = 4.1 for C282Y heterozygosity (95% CI 2.9 to 5.8, with heterogeneity in study results, making this association uncertain); and OR = 1.6 for H63D heterozygosity (95% CI 1 to 2.6, AF = 0.03). Estimates of penetrance for the C282Y/C282Y genotype were highly sensitive to estimates of the prevalence of iron overload disease. At a prevalence of 2.5 per 1000 or less, penetrance of the C282Y/C282Y genotype is unlikely to exceed 50%. Penetrance of other HFE genotypes is much lower. CONCLUSIONS: C282Y homozygosity confers the highest risk for iron overload but the H63D mutation is also associated with increased risk. Our data indicate a gradient of risk associated with different HFE genotypes and thus suggest the presence of other modifiers, either genetic or environmental, that contribute to the clinical expression of hemochromatosis.

Amino Acid Substitution↗
PubMed2002

Hepatitis C virus infection in Jordanian haemodialysis units: serological diagnosis and genotyping.

The seroprevalence and genotypes of hepatitis C virus (HCV) were studied in 283 patients attending six haemodialysis units in Jordan. In all, 98 (34.6%) patients were anti-HCV-positive by EIA, 92 (93.9%) of whom were also reactive in an immunoblot assay. The prevalence of anti-HCV was correlated with a history of blood transfusion before the introduction of blood donor screening for HCV and with duration of haemodialysis. HCV RNA was detected in 30 (30.6%) of 98 anti-HCV-positive sera. HCV viraemia was not associated with a particular antibody for the six HCV antigens studied by the immunoblot assay, although reactivity to the core antigens was greater in the HCV RNA-positive sera than in negative sera. Two HCV genotypes (1 and 4) were identified for the first time in Jordan by restriction fragment length polymorphism analysis of HCV 5'-NCR. The predominant genotype was HCV la (12 of 30). Genotypes lb and 4 were detected in 10 and 8 patients, respectively. The antibody response to HCV antigens was genotype-dependent, with a wider range of antibody specificities detected in the immunoblot assay in the 12 patients with genotype 1a infection than in the 8 patients with genotype 4. However, there was no significant difference in the prevalence of antibodies to HCV antigens among patients infected with either genotype 1a or lb. In conclusion, the prevalence of anti-HCV, blood transfusion, duration of dialysis and HCV genotypes suggest possible nosocomial HCV transmission among patients which needs confirmation by phylogenetic analysis of subgenomic HCV regions.

Adolescent↗