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PubMed1999

Metrifonate treatment of AD: influence of APOE genotype.

OBJECTIVE: To investigate whether an interaction exists between APOE genotype and the response of AD patients to metrifonate treatment and whether APOE genotype independently affects the rate of AD progression. BACKGROUND: Metrifonate is a new acetylcholinesterase inhibitor for the treatment of AD symptoms. METHODS: Data were pooled from four prospective, randomized, double-blind, placebo-controlled clinical trials and analyzed retrospectively. A total of 959 patients who received once-daily placebo (n = 374) or metrifonate (30 to 60 mg based on weight or a 50-mg fixed dose, n = 585) for up to 26 weeks agreed to APOE genotyping. RESULTS: Metrifonate clearly improved the cognitive performance of the AD patients when compared with placebo (Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS-Cog], p = 0.0001). The interaction of APOE genotype and the metrifonate effect on cognitive performance were not significant (p = 0.25). Metrifonate also clearly improved the global function of the AD patients when compared with placebo (Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus], p = 0.0001). The interaction of APOE genotype with the metrifonate effect on global function also was not significant (p = 0.70). No significant three-way interactions were observed among APOE genotype, gender, and response to metrifonate treatment (ADAS-Cog, p = 0.68; CIBIC-Plus, p = 0.26). APOE genotype did not influence disease progression as evaluated by either cognitive performance (ADAS-Cog, p = 0.93) or global function (CIBIC-Plus, p = 0.64). CONCLUSIONS: The findings from these studies of up to 26 weeks' duration do not clearly support an interaction between APOE genotype and metrifonate treatment effects. They suggest that APOE genotypes do not necessarily predict an AD patient's response to metrifonate treatment and that APOE genotype may not influence the rate of disease progression for patients with mild to moderate AD.

Aged↗
PubMed2000

The protective effect of hormone-replacement therapy on fracture risk is modulated by estrogen receptor alpha genotype in early postmenopausal women.

Genetic factors regulate bone mineral density (BMD) and possibly development of osteoporosis. It has been suggested that estrogen receptor alpha (ERalpha) genotype is associated with BMD, but the association between ERalpha genotype, fracture risk, and postmenopausal hormone replacement therapy (HRT) has not been studied. Therefore, we evaluated whether ERalpha polymorphism is associated with fracture risk in a 5-year trial with HRT in a population-based, randomized group of 331 early postmenopausal women. The participants consisted of two treatment groups: the HRT group (n = 151) received a sequential combination of 2 mg of estradiol valerate (E2Val) and 1 mg of cyproterone acetate with or without vitamin D3, 100-300 IU + 93 mg calcium as lactate per day; and the non-HRT group (n = 180) received 93 mg of calcium alone or in combination with vitamin D3, 100-300 IU/day. All new symptomatic, radiographically defined fractures were recorded. Pvu II restriction fragment length polymorphism of the ERalpha was determined using polymerase chain reaction (PCR). In all, 28 women sustained 33 fractures during the approximately 5.1-year follow-up. In the HRT group, the ERalpha genotype (PP, Pp, and pp) was not significantly associated with fracture risk (p = 0.138; Cox proportional hazards model). When the genotype was dichotomized (PP + Pp vs. pp), the incidence of new fractures in the HRT group was significantly reduced in women with the P allele (p = 0.046) with the relative risk (HR) of 0.25 (95% CI, 0.07-0.98), in comparison with the non-P allele group. After adjustment for time since menopause and previous fracture, the association between the dichotomous genotype and fracture risk persisted with HR of 0.24 (95% CI, 0.06-0.95;p = 0.042). In the non-HRT group, the ERalpha genotype was not significantly associated with fracture risk. During HRT, women with the pp genotype have a greater fracture risk than those with the P allele. The results suggest that the pp genotype is a relatively hormone-insensitive genotype, and it appears that women with the P allele may benefit more from the protective effect of HRT on fracture risk than women with the pp genotype.

Androgen Antagonists↗
PubMed2000

Association of transforming growth factor beta1 genotype with therapeutic response to active vitamin D for postmenopausal osteoporosis.

Transforming growth factor beta (TGF-beta) is an important regulator of bone metabolism, its effects being intertwined with those of estrogen and vitamin D. A T-->C polymorphism in exon 1 of the TGF-beta1 gene, which results in the substitution of proline for leucine, is associated with bone mineral density (BMD). However, it is not known whether this polymorphism affects the response to treatment with active vitamin D or to hormone replacement therapy (HRT) in individuals with osteoporosis. Changes in BMD at the lumbar spine (L2-L4 BMD) were compared among TGF-beta1 genotypes in 363 postmenopausal Japanese women who were divided into three groups: an untreated, control group (n = 130), an active vitamin D treatment group (n = 117), and an HRT group (n = 116). TGF-beta1 genotype was determined with an allele-specific polymerase chain reaction assay. In the control group, the rate of bone loss decreased according to the rank order of genotypes TT (homozygous for the T allele) > TC (heterozygous) > CC (homozygous for the C allele), with a significant difference detected between the CC and TT genotypes. The positive response of L2-L4 BMD to HRT increased according to the rank order of genotypes TT < TC < CC, although the differences among genotypes were not statistically significant. Individuals with the CC genotype responded to active vitamin D treatment with an annual increase in L2-L4 BMD of 1.6%, whereas those with the TT or TC genotypes similarly treated lost bone to a similar extent as did untreated subjects of the corresponding genotype. These results suggest that TGF-beta1 genotype is associated with both the rate of bone loss and the response to active vitamin D treatment.

Aged↗
PubMed2006

Diagnosis of alpha-1-antitrypsin deficiency: An algorithm of quantification, genotyping, and phenotyping.

BACKGROUND: Laboratory testing in suspected alpha-1-antitrypsin (A1AT) deficiency involves analysis of A1AT concentrations and identification of specific alleles by genotyping or phenotyping. The purpose of this study was to define and evaluate a strategy that provides reliable laboratory evaluation of A1AT deficiency. METHODS: Samples from 512 individuals referred for A1AT phenotype analysis were analyzed by quantification, phenotype, and genotype. A1AT concentrations were measured by nephelometry. Phenotype analysis was performed by isoelectric focusing electrophoresis. The genotype assay detected the S and Z deficiency alleles by a melting curve analysis. RESULTS: Of the 512 samples analyzed, 2% of the phenotype and genotype results were discordant. Among these 10 discordant results, 7 were attributed to phenotyping errors. On the basis of these data we formulated an algorithm, according to which we analyzed samples by genotyping and quantification assays, with a reflex to phenotyping when the genotype and quantification results were not concordant. Retrospective analyses demonstrated that 4% of samples submitted for genotype and quantitative analysis were reflexed to phenotyping. Of the reflexed samples, phenotyping confirmed the genotype result in 85% of cases. In the remaining 15%, phenotyping provided further information, including identifying rare deficiency alleles and suggesting the presence of a null allele, and allowed for a more definitive interpretation of the genotype result. CONCLUSIONS: The combination of genotyping and quantification, with a reflex to phenotyping, is the optimal strategy for the laboratory evaluation of A1AT deficiency.

Algorithms↗
PubMed2006

Co-circulation of genotypes IA and IB of hepatitis A virus in Northeast Brazil.

The Northeast region is the location of most cases of acute hepatitis A virus (HAV) in Brazil. In the present study, the genotypes of HAV strains from Pernambuco State, one of most populous states in the Northeast region, were characterized. Blood samples positive for anti-HAV IgM from 145 individuals (mean age = 29.1 years), collected during 2002 and 2003, were submitted to nested RT-PCR for amplification of the 5'non-translated region (5'NTR) and VP1/2A regions of the HAV genome. The VP1/2A and 5'NTR regions were amplified in 39 and 21% of the samples, respectively. Nucleotide sequencing was carried out in 46% of VP1/2A and in 53% of 5'NTR isolates. The identity in nucleotide sequence of the VP1/2A region ranged from 93.6 to 100.0%. Phylogenetic analysis of the VP1/2A sequences showed that 65% belong to sub-genotype IA and 35% to sub-genotype IB. Co-circulation of both sub-genotypes was observed in the two years studied. Distinct clusters of highly related sequences were observed in both sub-genotypes, suggesting endemic circulation of HAV strains in this area. In the 5'NTR isolates, 92.7-99.2% identity was observed and two isolates presented one deletion at position 413. Phylogenetic analysis showed that genotype IA strains cluster in the tree in the same way as genotype IB strains, but one IIIA isolate from Spain clusters with genotype IB strains. These results do not allow us to state that 5'NTR could be used to genotype HAV sequences. This is the first report of co-circulation of sub-genotypes IA and IB in this region, providing additional information about the molecular epidemiology of HAV strains in Brazil.

5' Untranslated Regions↗
PubMed2001

Retrospective evaluation of the influence of the interleukin-1 genotype on radiographic bone levels in treated periodontal patients over 10 years.

BACKGROUND: A difference in genetic susceptibility to plaque accumulation has been advocated to explain different responses to periodontal therapy. The purpose of this study is to assess the role of the interleukin-1 (IL-1) polymorphism on the rate of bone and tooth loss in non-smoking periodontally treated patients during maintenance. METHODS: Sixty consecutive non-smoking patients (mean age 46.8 +/- 5.0) with moderate to severe periodontitis, treated and maintained for over 10 years were selected. At baseline (T0), radiographic evaluation (cemento-enamel junction [CEJ]-root apex, CEJ-bottom of defect mesial and distal, CEJ-bone crest mesial and distal, crown-root ratio) was performed. All patients received scaling and root planing; 36 patients then underwent surgical therapy. Subsequently, all patients were enrolled in a periodontal maintenance program with recall visits every 3.4 +/- 1.0 months for at least 10 years. At the latest recall visit (T2) the same radiographic measurements evaluated at baseline were taken and a DNA sample for IL-1 genetic susceptibility testing was collected and sent for analysis. RESULTS: Twenty-three of the 60 patients (38.3%) were IL-1 genotype positive. A total of 52 teeth (3.3%) out of 1,566 were lost due to periodontitis between T0 and T2; 28 of 957 (2.9%) in the IL-1 genotype negative group and 24 of 609 (3.9%) in IL-1 genotype positive group. The mean variation in bone defect level (DeltaBD) averaged -0.04 mm in IL-1 genotype negative patients and 0.01 mm in IL-1 genotype positive patients. The mean variation in bone crest level (DeltaBC) averaged -0.24 mm in IL-1 genotype negative patients and -0.28 mm in IL-1 genotype positive patients. However, a few patients showed significant differences in response to therapy based on initial bone levels and genotype. IL-1 negative patients who showed minimal initial bone loss responded to the therapy better than the IL-1 positive patients. IL-1 positive patients with severe initial bone loss showed a better response to the therapy than IL-1 negative patients. CONCLUSIONS: On average, there were no significant differences related to IL-1 genotype in tooth loss after 10 years in a non-smoking, well-maintained periodontal population. On an individual patient basis, the IL-1 genotype, in combination with the initial bone level, seems useful at the beginning of therapy for predicting bone level variation.

Adult↗
PubMed2004

Effect of the interleukin-1 genotype on outcomes of regenerative periodontal therapy with bone replacement grafts.

BACKGROUND: Previous studies have shown an association between a specific genotype for the inflammatory cytokine interleukin (IL)-1 and the severity of periodontal disease. The purpose of this study was to evaluate the effect of the IL-1 genotype on the outcomes of periodontal surgical regenerative treatment with bone replacement grafts. METHODS: Forty-four patients with interproximal intrabony defects were treated with bone replacement grafts. Probing depths (PD) and clinical attachment levels (CAL) were measured before treatment and at least 9 months post-treatment. Whole-mouth plaque index (WMPI) and bleeding index (WMBI) were recorded as well. All patients were tested for the IL-1 genotype. RESULTS: Thirteen (29.55%) of the patients were IL-1 genotype positive. There was no statistically significant difference between the genotype-positive and genotype-negative groups regarding age, smoking status, gender, WMPI, and WMBI. There was no significant difference in PD or CAL between the genotype-positive and genotype-negative groups at baseline. Genotype-positive patients had a smaller reduction in probing depth (1.86 mm versus 2.13 mm) and a greater gain of clinical attachment (1.20 mm versus 0.65 mm). These differences were not statistically significant (P = 0.70, P = 0.40). Multivariate regression analysis showed that presurgical PD significantly influenced post-surgical PD and CAL, and only WMPI significantly influenced CAL. CONCLUSION: In this study, there was no evidence that the IL-1 genotype influences the clinical treatment outcomes of regenerative periodontal therapy with bone replacement grafts.

Adult↗
PubMed2002

Utility and accuracy of template-directed dye-terminator incorporation with fluorescence-polarization detection for genotyping single nucleotide polymorphisms.

There are little independent data available about how well single nucleotide polymorphism (SNP) genotyping technologies perform in the typical molecular genetics laboratory. We evaluated the utility and accuracy of a widely used technology, template-directed dye-terminator incorporation with fluorescence-polarization detection (FP-TDI), in a sample of 177 SNPs selected solely on the basis of map location. Genotypes were generated without optimization using standard protocols. Overall, 81% of the SNPs we studied generated readable genotypes by FP-TDI. Thirty-two SNPs were genotyped in duplicate by PCR-RFLP orfluorescent dye-terminator sequencing. Out of a total of 631 duplicate genotypes, no true discrepancies were detected. The true error rate has a 95% chance of lying between 0 and 6 out of 1000 genotypes. We also tested for deviations from Hardy-Weinberg Equilibrium in 33 SNPs genotyped in 50 unrelated individuals, and no significant deviations were detected. Our FP-TDI data were readily adaptable to automated genotype calling using our own method of cluster analysis, which assigns a probability score to each genotype call. We conclude that FP-TDI is both efficient and accurate. The method can easily fill the needs of SNP genotyping projects at the scale typically used for regional or candidate-gene association studies.

Fluorescence Polarization↗
PubMed2005

The effect of aging on the relationship between the cytochrome P450 2C19 genotype and omeprazole pharmacokinetics.

BACKGROUND AND OBJECTIVE: The metabolic activity of cytochrome P450 (CYP) 2C19 is genetically determined, and the pharmacokinetics of omeprazole, a substrate for CYP2C19, are dependent on the CYP2C19 genotype. However, a discrepancy between the CYP2C19 genotype and omeprazole pharmacokinetics was reported in patients with liver disease or advanced cancer. The objective of the present study was to evaluate the effect of aging on the relationship between the CYP2C19 genotype and its phenotype. METHODS: Twenty-eight elderly and 23 young Japanese volunteers were enrolled after being genotyped. Each subject received a single intravenous dose of omeprazole (10 mg and 20 mg for the elderly and the young groups, respectively) and blood samples were obtained up to 6 hours after dose administration to determine the plasma concentrations of omeprazole and its metabolites, 5-hydroxyomeprazole and omeprazole sulfone. Pharmacokinetic parameters were obtained by noncompartmental analysis. Linear regression models were used to examine the joint effects of covariates such as genotype, age, etc., on the pharmacokinetic parameters, and the pharmacokinetic parameters showing statistical significance were compared by ANOVA. RESULTS: There were significant differences between genotypes in the area under the plasma concentration-time curve of the young group and the elderly group. The number of mutation alleles and age were significant covariates for systemic clearance (CL), but age was the only significant covariate for volume of distribution at steady state (Vss). There were significant age- and genotype-related differences and a significant age x genotype interaction in CL (20.6+/-11.0/12.7+/-4.0/3.2+/-1.0 and 5.4+/-4.0/3.7+/-1.4/2.1+/-0.7 L/h for homozygous extensive metabolisers [EMs]/heterozygous EMs/poor metabolisers [PMs] of the young and the elderly groups, respectively). In Vss, a significant difference was found between the young and the elderly groups (219+/-115 and 107+/-44.5 mL/kg, respectively), but not between three genotypes (178+/-142, 173+/-79 and 110+/-51 mL/kg for homozygous EMs, heterozygous EMs and PMs, respectively). CONCLUSION: The elderly EMs showed wide variance in the in vivo CYP2C19 activity and were phenotypically closer to the elderly PMs than the young EMs were to the young PMs. Some of the elderly homozygous EMs, as well as heterozygous EMs, have a metabolic activity similar to PMs, and the CYP2C19 genotype may therefore not be as useful as phenotyping in the elderly.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Conjugated linoleic acid improves feed efficiency, decreases subcutaneous fat, and improves certain aspects of meat quality in stress-genotype pigs.

Conjugated linoleic acid (CLA) was supplemented to crossbred growing-finishing barrows (n = 60) at 0.75% of the total diet. Pigs were randomly assigned to the CLA or control diets based on stress genotype (negative, carrier, or positive). Gain:feed was higher for CLA diet animals (350 g/kg feed) than for control diet animals (330 g/kg feed) independent of genotype (P < 0.05). No differences were observed for ADG for the diets (P = 0.71) or genotype classes (P = 0.40). Postmortem pH was lower (P < 0.01) by 3 h for CLA-supplemented pigs, with no differences in ultimate pH. No differences (P = 0.16) were observed for ultimate pH between the three genotypes. Conjugated linoleic acid-supplemented pigs exhibited less 10th rib fat depth (2.34 cm vs 2.84 cm) and last rib fat depth (2.46 cm vs 2.72 cm) than control pigs (P < 0.05). Loin muscle area (LMA) was not affected (P = 0.18) by CLA supplementation, but LMA was different (P < 0.02) for genotype; positive genotype carcasses had the largest LMA (45.02 cm2) and negative carcasses had the smallest LMA (36.44 cm2). Carrier carcasses were intermediate for LMA (40.76 cm2). Subjective scores for color were not affected (P = 0.98) by CLA but color was different (P < 0.01), with scores of 1.50, 2.40, and 3.1 for positive, carrier, and negative genotypes, respectively. Subjective marbling scores were increased (P < 0.03) in all genotypes with CLA supplementation. Subjective firmness scores were higher (P < 0.06) for CLA-supplemented pigs and were highly correlated (0.89) to marbling scores. The L* values were higher (P < 0.01) for stress-positive pigs at 24 h postmortem. Also, L* values were higher (P < 0.01) for CLA-fed pigs over 7 d of shelf storage. Sensory characteristics were not different with CLA supplementation for tenderness (P = 0.24), juiciness (P = 0.35), or flavor intensity (P = 0.14). This study showed that LMA was increased with stress-carrier and stress-positive genotypes, but lean color was negatively affected with the presence of the stress gene. Conjugated linoleic acid supplementation improves feed efficiency, decreases backfat, and improves pork quality attributes of marbling and firmness of the longissimus muscle. Furthermore, there is seemingly no interaction between the stress-genotype status of pigs and the subsequent effect of CLA on their growth and performance.

Adipose Tissue↗
PubMed2003

Dopamine transporter genotype influences the attention deficit in Korean boys with ADHD.

Attention appears to be inheritable, stable and influenced by genetic factors. The use of the Continuous Performance Test (CPT), as an endophenotypic measure, is valuable for genetic studies because it may show increased sensitivity to specific dimensions in attention deficit hyperactivity disorder. However, few studies have been designed to examine the influence of the genotype on attention level measured by CPT in ADHD patients. This study examinee the difference between 10/10 and 10/* genotype in the attention deficits measured by the CPT in ADHD patients. Forty-four unrelated ADHD patients were recruited from the psychiatric outpatients' clinic at Kangbuk Samsung Hospital. Two child psychiatrists made the diagnoses of ADHD using the DSM- IV diagnostic criteria. The genomic DNA was extracted from the blood, and analyzed to determine the genotype. A 40- base pair variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region was amplified. The attention deficits were measured by the test of variables of attention (T.O.V.A.). Between the 10/10 genotype and 10/* genotype, standard scores of the T.O.V.A were compared using a Mann-Whiney test. A comparison with the 10/10 genotype and 10/* genotype showed that those patients with the 10/10 genotype made less omission errors in the first quarter of the test (p < 0.05, by Mann-Whiney test). No significant differences were observed in the errors of commission, response time, variability. This study found that the 10/10 genotype made less omission errors on the T.O.V.A. This suggests that the dopamine transporter genotype influences the attention deficits measured by T.O.V.A.

3' Untranslated Regions↗
PubMed1998

Study of hepatitis C virus genotype in Guizhou area of southwestern China.

OBJECTIVE: To determine the concordance in various hepatitis C (HCV) genotyping methods and to investigate the distribution of HCV genotypes in Guizhou area of Southwest China. METHODS: Serum samples from 206 patients (100 with chronic hepatitis and 106 with hemopathy) were detected for antibody of HCV by second generation enzyme-labelled immunosorbent assay (ELISA). Thirty-five anti-HCV positive samples were detected for HCV RNA by RT-polymerase chain reaction (PCR) and 30 HCV RNA positive samples were determined for their genotypes by three various genotyping methods [PCR with type-specific primers at the core region (primer-set), slot-blot hybridization with type-specific probes at NS5B region (blotting) and the restric fragment length polymorphism analysis of PCR products of 5' NC region (RFLP)]. Ten samples with the known genotype were analysed by the direct sequencing. RESULTS: Of 30 samples with positive HCV RNA, the types of 22 could be classified by three methods, and the genotypes determined by various methods had complete concordance. The types of 6 samples could be classified by two methods and 5 had agreement subtypes. The types of two samples could be classified only by RFLP. Overall, 27 (90.0%) had subtype 1b infection and 3 (10.0%) had subtype 2a infection. The nucleotide sequence of 8 samples with subtype 1b and one with subtype 2a were analysed by the direct sequencing. The subtypes determined by sequence analysis were in complete concordance with those decided by various genotyping methods. CONCLUSIONS: Subtype 1b is the predominent HCV genotype in Guizhou area, while subtype 2a is less common. There was a good concordance with the genotyping results obtained by various HCV genotyping methods.

Antibodies, Viral↗
PubMedDate not supplied

[HCV genotypes. Liver histopathology and immunologic profile in four groups of patients].

AIM: Study on the prevalence of MCV genotypes, and correlation with liver pathology and immunological parameters. PATIENTS AND METHODS: 77 chronic hepatitis C patients (52 males, 25 females), mean age 44 +/- 14 years, belonging to four groups: (1) 23 (11 males) without other aetiology, (II) 19 (18 males) excessive drinkers, (III) 18 (12 males) haemodialysed, (IV) 17 (11 males) renal transplantation patients Genotyping was done by PCR (primers of the core, and hybridisation with specific probes). Serum Igs A, G, and M (by nephelometry), and peripheral blood lymphocyte (PBL) subsets (by flow cytometry) were determined. RESULTS: One genotype was found in 62 patients (1b 69.2%, 1a 21.5%, 2a 3.1%, 2b 3.1%, 3a 9.2%), and two genotypes in 4 patients (1b + 3a in 1 of group 1, 1b + 2a in 2 and 1a + 3a in 1 of group 111). Twelve cases (15.6%) were not identified (NI). Relative prevalence was not different in the four groups, but in 7 drug addicts 1 b was not found (Ia in 71.4%, 3 a 28.6%) The relationship between genotypes and age was significant (p < 0.05): in the 34 patients with less than 40 years, 1b was found in 38.2%, in the others in 41.2%, and NI in 20.6%; in those with 40-60 years, 1b was found in 68.8%, in the others in 15.6%, M in 15.6%; in those above 60 years, 1b was found in 90.9%, in the others in 9.1%. Of those identified, only genotype 1 (1a and 1b) was associated to moderate or severe activity, and infected 11/13 cases of cirrhosis or severe fibrosis. IgM (g/dL) was lower in 1b than in the others: 1.58 + 1.23 vs. 2.53 + 1.93 (p < 0.01). PBL (per mm3) were lesser in 1b than in the others, with significance for the CD8+: 540t239 vs. 739 + 420 (p < 0.01). CONCLUSIONS: Genotype 1b was the most prevalent in Portuguese patients, more significantly in the elderly, and was absent in drug addicts. The prevalence of genotypes is similar in general patients, in chronic haemodialysed, in renal transplantation recipients and in alcoholics. More severe liver pathology was associated with 1b and 1a genotypes. IgM and CD8+ had lower mean values in 1b infected patients. Other genotypes are certainly important in Portugal.

Adolescent↗
PubMed2001

[Hepatitis C virus genotypes. Study of 302 patients coinfected by the human immunodeficiency virus].

BACKGROUND: To study the distribution of different HCV genotypes in HIV-infected patients. PATIENTS AND METHOD: This study was carried out in 302 HIV/HCV-coinfected patients who were followed-up at the HIV/AIDS Unit of the Arnau de Vilanova University Hospital of Lleida (Spain). HCV genotypes were determined by Inno-Lipa HCV II technique (Innogenetics, Belgium). RESULTS: 143 patients (51.43%) had a genotype-1, followed by genotype-3 (81 patients; 29.13%), genotype-4 (53 patients; 19.06%), and genotype-2 (one patient; 0.35%). It was not possible to know the genotype in 24 patients (NT). CONCLUSIONS: In our health care area, HCV genotype-1 was the commonest among HIV/HCV-coinfected patients. However, a given HIV-infected patient with HCV antibodies has practically the same probability of having a genotype-1 as a genotype non-1.

Genotype↗
PubMed2000

[Epidemiological aspects of the genotype of hepatitis C virus].

OBJECTIVE: To research the epidemiological characteristics of genotype of hepatitis C virus. METHODS: 107 HCV isolates from 7 cities in southern, northern and northeast of China were analyzed using PCR and second generation line probe assay (INNO-LiPA). RESULTS: The analysis of HCV genotypes showed that: 1. HCV l b was the common genotype (83 17%), however the frequency of genotype l b in northeast (72.22%) was lower than northern (87.65%, P <0.01), and the frequency of the genotype 2 was in low level (6.86%). The rate of coinfection with l b and other genotype was 10.29%. 2. The rate of infection with genotype l b in female patients was higher (93.61%) than that in male (75.0%) showing statistical significance (P <0.01). 3. In three age groups (< 30, 30 - 49 and > 50 years old) the rates of infection with genotype l b were 77.77%, 83.92% and 90.90%, respectively. 4. The detection rates of genotype l b in patients with infection period > 10 years and <10 years were 100% and 80.43% respectively (P <0.01). CONCLUSIONS: There are some relationship between HCV genotype and HCV geographic distribution, sex, age and infection period of patients.

Adolescent↗
PubMed2001

Hepatitis C viral genotype influences the clinical outcome of patients with acute posttransfusion hepatitis C.

Most patients with an acute infection of hepatitis C virus (HCV) will develop chronic hepatitis, and only about 15-20% of the cases will resolve spontaneously. The mechanism for the different outcomes in patients with acute HCV infection remains unclear. HCV genotype has been recognized as an important factor affecting the clinical course and outcome of chronic hepatitis C patients. In order to evaluate the role of HCV genotype in the clinical course and outcome of acute posttransfusion hepatitis C, 67 patients with acute posttransfusion hepatitis C from a prospective study of posttransfusion non-A, non-B hepatitis were enrolled. Thirty-nine patients (58.2%) were HCV genotype 1b. Among the 67 patients with acute posttransfusion hepatitis C, 53 (79.1%) progressed to chronic hepatitis. Significantly more patients with genotype 1b than non-1b genotypes developed chronic hepatitis (89.7% vs. 64.3%; P = 0.019). There was no significant difference in gender, mean age, amount of transfused blood, hepatitis symptoms, jaundice, incubation period, peak serum alanine transaminase, or serum HCV RNA titer between patients with HCV genotype 1b and non-1b infections. Patients who developed chronic hepatitis had a significantly greater incidence of genotype 1b infection (66.0% vs. 28.6%; P = 0.013) and a longer incubation period (7.3 weeks vs. 5.4 weeks; P = 0.052) than patients whose infection was resolved. Patients with a genotype 1b infection that resolved itself spontaneously all had an incubation period of less than 6 weeks. Multivariate logistic regression analysis revealed that genotype 1b and an incubation period > or = 6 weeks were significant predictive factors for the development of chronic hepatitis. Therefore, the HCV genotype can influence the outcome of patients with acute HCV infection.

Acute Disease↗
PubMed2001

[Distribution of hepatitis C virus genotypes among the hemodialysis population in the province of Alicante].

UNLABELLED: Hepatitis C virus (HCV) genotypes are irregularly distributed among the different geographic area and groups at risk. OBJECTIVE: To study the different HCV genotypes and subtypes of hemodialyzed patients from Alicante. METHODS: We studied 640 patients on haemodialysis (HD) and we determined the RNA-HCV and the genotypes in the 120 patients with antibodies against HCV (HCV-Ab). We compared the results with the genotypes of 1,370 patients from other groups at risk in the same geographic area. RESULTS: RNA-HCV was not found in the serum in 15% (18/120) of the patients on HD who were HCV-Ab positive. Prevalence of the different genotypes in the 102 patients with positive viral RNA was the following: 1b: 56.8% (58/102), 1a: 19.6% (20/102), 3: 17% (17/102), 2a-2c: 1.9 (2/102), 2b: 0.9% (1/102) 4: 2.9 (3/102), 5: 0.9% (1/102). In conclusion, the genotype 1b was the most frequent in the patients studied in all these areas, and was the same as in the rest of the country. This genotype has been associated with the most severe hepatic disease and poor response to treatment, affecting the prognosis of these patients. The most frequent genotypes in HD in Alicante were 1b, 3 and 1a. HCV genotypes distribution among the HD units was not uniform in the different geographic areas. HCV genotypes distribution in the HD population is similar to other groups at risk from the same geographic area.

Adult↗
PubMed2002

[Application of multiplex PCR in genotyping of hepatitis B virus prevailing in Guangdong Province of China].

OBJECTIVE: To establish a convenient method for the genotyping of hepatitis B virus (HBV) using multiplex PCR. METHOD: Based on the alignment of 114 complete nucleotide sequences of HBV DNA belonging to different genotypes, acquired from the GenBank, genotype-specific sequences were identified according to which 6 pairs of primers were designed corresponding to each genotype. Subsequent genotyping of HBV was performed using these primers that were added, either alone or in conjunction with others, into a multiplex PCR reaction tube, and HBV genotype was determined according to the length of amplified DNA. RESULT: The genotyping result of multiplex PCR was consistent with that produced by PCR- restriction fragment length polymorphism as established by Lindh. We found in this study that among the HBV carriers in the vicinities Guangzhou of City, about 45% belonged to B genotype, 38.75% to C genotype and 16.75% to D genotype. CONCLUSION: This multiplex PCR method is simple, convenient and more differential.

China↗