Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study

Summary.  This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype ( P  = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.     

Relationship of genotypes of hepatitis B virus to mutations, disease progression and response to antiviral therapy

SUMMARY: Phylogenetic analysis has led to the classification of hepatitis B virus into eight genotypes, designated A to H. The genotypes have differences in biological properties and show heterogeneity in their global distribution. These attributes of the genotypes may account not only for differences in the prevalence of hepatitis B virus mutants in various geographic regions, but also be responsible for differences in the clinical outcome and response to antiviral treatment in different population groups.     

Frequency of the HFE C282Y and H63D mutations in Danish patients with clinical haemochromatosis initially diagnosed by phenotypic methods

AIM: To assess the frequency of the C282Y and H63D mutations on the HFE gene in Danish patients with clinical hereditary haemochromatosis initially diagnosed by phenotypic methods. METHODS: In the period 1950-1985, an epidemiological survey in Denmark identified 179 patients with clinical idiopathic haemochromatosis diagnosed by phenotypic methods (serum transferrin saturation, serum ferritin, liver biopsy and mobilisable body iron stores). In 32 unrelated patients, frozen blood samples were available for genetic analysis. In a subsequent series of 26 unrelated Danish patients, a phenotypic diagnosis of clinical idiopathic haemochromatosis was made before blood samples were taken for HFE genotyping. The total series consisted of 58 patients (40 men and 18 women) with a median age of 60 yrs (range 18-74). HFE genotyping was performed by the polymerase chain reaction (PCR) technique. RESULTS: Among the patients, 55 of 58 (94.8%) were C282Y/C282Y homozygous. One 63-year-old woman (1.7%) was compound C282Y/H63D heterozygous. Two women (3.4%), aged 42 and 43 yrs were negative for both the C282Y and the H63D mutation. CONCLUSION: In the Danish population, homozygosity for the C282Y mutation appears to be the prevailing cause of clinically overt genetic haemochromatosis. This finding has implications both for the evaluation of patients with iron overload disorders and for the strategy in future population screening surveys.     

185株白念珠菌25S rDNA基因型分布特点

目的：研究临床不同来源白念珠菌25S rDNA基因型分布特点,探讨白念珠菌不同基因型与感染部位或不同感染类型之间的联系.方法：特异性扩增不同来源的185株白念珠菌25S rDNA基因Ⅰ型内含子序列,再经过琼脂糖凝胶电泳方法对扩增条带进行基因分型,并对不同感染部位、不同感染类型的白色念珠菌的基因型进行比较.结果：185株白念珠菌中,A型122株（65.9％）、B型35株（18.9％）和C型28株（15.1％）,未发现D型与E型菌株;外阴阴道念珠菌病（VVC）来源与深部组织来源的白念珠菌25S rDNA基因型差异具有统计学意义（P=0.000）;深部组织来源菌株中,艾滋病相关性和非艾滋病相关性白念珠菌基因型差异无统计学意义（P=0.680）.结论：VVC来源和深部组织来源的白念珠菌25S rDNA基因型不同,而深部组织来源的艾滋病相关性和非艾滋病相关性白念珠菌25S rDNA基因型相同.     

Genetic variants of apolipoprotein A5 T-1131C and apolipoprotein E common polymorphisms and their relationship to features of metabolic syndrome in adult dyslipidemic patients

Objectives

The aim was to evaluate the relationships of the T-1131C (rs662799) polymorphism variants of apolipoprotein A5 (Apo A5) gene and variants of apolipoprotein E (Apo E) gene common polymorphism (rs429358, rs7412) to signs of metabolic syndrome (MetS).

Design and methods

We examined 590 asymptomatic dyslipidemic patients divided into MetS + (n = 146) and MetS − (n = 444) groups according to criteria of NCEP ATPIII Panel. We evaluated genotype frequencies and differences in MetS features between individual groups. Logistic regression analysis was used for the evaluation of Apo A5/Apo E variants as possible risk factors for MetS.

Results

We found no statistical differences between genotype and allele frequencies for both Apo A5 and Apo E polymorphisms between MetS + and MetS − groups. In all subjects and MetS − group, we confirmed well-known association of the − 1131C Apo A5 minor allele with elevated triglycerides (TG, p < 0.001). The Apo E gene E2 and E4 variants were associated with higher levels of TG (p < 0.01) in comparison to E33 common variant. However, no statistical differences were observed in MetS + subjects, regardless of significantly higher TG levels in this group. Apo A5/Apo E variant analysis in all dyslipidemic patients revealed significant increase of TG levels in all subgroups in comparison to common − 1131T/E3 variant carriers, the most in − 1131C/E4 variant subgroup. Logistic regression analysis models showed no association of Apo A5, Apo E and all Apo A5/Apo E variants with metabolic syndrome, even after adjustment for age and sex.

Conclusion

Our study refined the role of Apo A5 and Apo E genetic variants in the group of adult dyslipidemic patients. We demonstrate that except of TG, Apo A5 T-1131C (rs662799) and Apo E (rs429358, rs7412) polymorphisms have no remarkable effect on MetS characteristics.     

Impact of HCV genetic differences on pathobiology of disease

Multiple HCV genotypes have been isolated worldwide. Genotype seems to be involved in the main pathological aspects of HCV infection. Insulin resistance, steatosis and progression toward cirrhosis, fibrosis and hepatocellular carcinoma establish and develop following genotype-specific mechanisms. Moreover genotype influences pharmacological treatment in term of dose and duration. Pathways involved in cell proliferation, apoptosis, lipid metabolism, insulin and interferon signaling are impaired to a different extent among genotypes, leading to distinct pathological settings. Genotype 1 is associated with a more aggressive disease with increased insulin resistance, worst response to therapy, higher risk of cirrhosis and hepatocellular carcinoma development, while genotype 3 is associated with increased steatosis and fibrosis. The identification and characterization of HCV types and subtypes provides insight into the different outcome of HCV infection and responsiveness to therapy. In the present article, we focused on the pathogenicity of HCV genotypes and their effect on disease progression and treatment.     

黏质沙雷菌随机扩增DNA多态性DNA分型

目的明确同一时间段先后分离自同一病房2例患者的两株黏质沙雷菌是否属于同源菌。方法应用随机扩增DNA多态性（RAPD）技术对同一时间段先后自同一病房2例患者痰液标本中分离得的2株黏质沙雷菌进行RAPD基因多态性分析。结果2株黏质沙雷菌扩增出2条不同的电泳带谱。结论2株黏质沙雷菌为不同的RAPD基因型,非同源菌。     

MBL,P2X7, and SLC11A1 gene polymorphisms in patients with oropharyngeal tularemia

Conclusion: A significant association was found of oropharyngeal tularemia with SLC11A1 allele polymorphism (INT4?G/C) and MBL2 C?+?4T (P/Q). These results indicate C allele and Q allele might be a risk factor for the development of oropharyngeal tularemia.

Aim: This study aimed to investigate the relationship of SLC11A1, MBL, and P2X₇ gene polymorphism with oropharyngeal tularemia.

Methods: The study included totally 120 patients who were diagnosed with oropharyngeal tularemia. Frequencies of polymorphisms in the following genes were analyzed both in the patient and control groups in the study: SLC11A1 (5’(GT)_n Allele 2/3, Int4?G/C, 3’ UTR, D543N G/A), MBL (MBL2 C?+?4T (P/Q), and P2X₇ (?762 C/T and 1513 A/C).

Results: Among all polymorphisms that were investigated in this study, SLC11A1 gene showed a significance in the distriburtion of polymorphism allelle frequency at the INT4 region. Frequency of C allele was 54 (28%) in patients with oropharyngeal tularemia, and 31 (13%) in the control group (p?=?0.006 and OR = 1.96 (1.21–3.20)). An association was detected between MBL2 C?+?4T (P/Q) gene polymorphism and oropharyngeal tularemia (p?7 (?762 C/T and 1513 A/C) gene polymorphism and oropharyngeal tularemia in this study (p?>?0.05).     

Effect of beta-globin gene cluster haplotype on the hematological and clinical features of sickle cell anemia

In 113 black American adults with sickle cell anemia (HbSS), we examined nine polymorphic restriction sites, including the Xmnl site 5' to the G gamma gene, to see whether haplotype is related to the level of HbF and the proportion of G gamma chains or if it influences the hematological and clinical features of the disease. Seventy-five percent of the patients were homozygous or heterozygous for the Benin (no. 19) or Central African Republic (Bantu, no. 20) haplotypes; 13.3% were homozygous or heterozygous for the Senegal (no. 3) haplotype, while 11.5% had other genotypes. Of the subjects, 14.2% were either homozygous or heterozygous for the Xmnl restriction site 5' to the G gamma gene. We found no effect of haplotype on HbF levels. The level of G gamma chains was 60.5% +/- 17.0% in individuals heterozygous or homozygous for haplotype no. 3 and was 46.9% +/- 11.6% in individuals with other haplotypes. Subjects with the Xmnl site 5' to the G gamma gene had G gamma globin levels of 59.5% +/- 16.7% while those lacking that site had an average of 47.2% +/- 12.1%. There were no significant differences among these groups in hemoglobin concentration, packed cell volume, mean cell volume, or clinical indicators of vaso-occlusive severity, including crises, hospitalizations per year, aseptic bone necrosis, acute chest syndrome, or leg ulcers. While the presence of haplotype 3 and the 5' G gamma Xmnl site were associated with increased G gamma chains, there was no effect on HbF level or other hematological and clinical features that might reflect disease severity. It is likely that determinants unrelated to haplotype, linked or unlinked to the beta-globin gene cluster, are the major effectors of differences in the levels of HbF in American patients with sickle cell anemia.     

Methylenetetrahydrofolate reductase genotypes, dietary habits and susceptibility to stomach cancer

Objective To study the relation among methylenetetrahydrofolate reductase (MTHFR) C677T genotypes, dietary habits and the risk of stomach cancer (SC). Methods A case-control study was conducted with 107 cases of SC and 200 population -based controls in Chuzhou district, Huaian. Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects, MTHFR genotypes were detected by PCR-RFLP. Results (1) The prevalence of the MTHFR C/T or T/T genotypes was found to be significantly different between controls (68.5%) and SC cases (79.4%. P =0.0416), the increased risk had an adjusted OR of 1.79 (95%CI: 1.01 -3.19). (2) Among subjects who had a low intake of garlic or Chinese onion, MTHFR C/T or T/T genotypes significantly increased the risk of developing SC. Among non-tea drinkers or among subjects who had a frequent intake of meat, the carriers of the MTHFR C/T or T/T genotypes had a higher risk of SC than individuals with the C/C type MTHFR. Conclusion The polymorphism of MTHFR C677T was associated with increased risk of developing SC, and that individuals with differing genotypes may have different susceptibilities to SC, based on their exposure level to environmental factors. This work was supported in part by a Grant-in Aid for International Scientific Research, Special Cancer Research (No.08042015, 11137311) from the Ministry of Education, Science, Sports, Culture and Technology, Japan.