Hepatitis C virus genotypes in a non-cirrhotic Italian population with chronic hepatitis C: correlation with clinical, virological and histological parameters. Results of a prospective multicentre study

To identify correlations between the distribution of hepatitis C virus (HCV) genotypes and demographic, pathological and virological parameters of HCV-infected patients, we prospectively recruited 650 patients with biopsy-proven chronic hepatitis C without histological aspects of cirrhosis; none had been treated with antiviral therapy. Data regarding gender, age, mode of HCV transmission, alanine aminotransferase (ALT) and HCV RNA levels, immunoglobulin M (IgM) anticore values, liver histology and histological activity were obtained from each patient and correlated on multivariate analysis with infecting HCV genotype. Fifty-five per cent of the patients were infected with HCV genotype 1, 20% with HCV genotype 2, 18% with HCV genotype 3 and 7% with HCV genotype 4. Non-transfusional HCV transmission, low ALT levels, IgM anticore reactivity and a low histological grading score were independent variables associated with HCV genotype 1. Older age, female gender, post-transfusional transmission and a high histological grading score were related to HCV genotype 2, whilst younger age, history of current/previous drug abuse, high ALT values, low IgM anticore reactivity and high viraemic levels were associated with HCV genotype 3. History of illicit use of intravenous drugs and low HCV RNA levels were the only independent variables correlated with HCV genotype 4. Genotype 1 remains predominant in Italy but the prevalence of HCV genotypes is changing in relation to age and mode of transmission: Italian patients with HCV genotype 3 are younger and exhibit higher levels of ALT and HCV RNA than patients with other genotypes.     

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.     

IL28B polymorphisms predict response to therapy among chronic hepatitis C patients with HCV genotype 4

Summary. Genetic polymorphisms near IL28B are associated with spontaneous and treatment‐induced clearance of hepatitis C virus (HCV). Our objective was to assess the predictive value of IL28B polymorphisms in the treatment of chronic hepatitis C of patients with HCV genotypes 4, for which data are currently limited. We analysed the association of IL28B polymorphisms with the virological response to treatment among 182 naïve chronic hepatitis C patients with HCV genotype 4, all from Syria. Associations of alleles with the response patterns were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. Sustained virological response (SVR) was achieved in 26% of rs8099917 TG/GG carriers compared with 60% of TT carriers (P < 0.0001) and 35% of rs12979860 CT/TT carriers compared with 62% of CC carriers (P = 0.0011). By multivariate analysis, the association between rs8099917 and SVR remained significant (OR = 0.19, 95% CI 0.07–0.50, for TG/GG vs TT, P = 0.0007), with the only significant covariate being advanced fibrosis (OR = 0.13, 95% CI 0.04–0.37, P = 0.0002). In conclusion, IL28B polymorphisms are the strongest predictors of response to therapy among chronic hepatitis C patients with HCV genotype 4.     

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.     

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.     

Genotypic and phenotypic analysis of Streptococcus mutans from different oral cavity sites of caries‐free and caries‐active children

Introduction: Streptococcus mutans exhibits extensive genotypic diversity, but the role of this variation is poorly understood. This study aimed to determine the number and distribution of genotypes of S. mutans isolated from caries‐active and caries‐free children and to evaluate some of their phenotypic traits. Methods: Stimulated saliva, tongue surface and biofilms over sound and carious teeth surfaces were sampled from 10 caries‐free and 11 caries‐active children aged 5–8 years. A total of 339 isolates of S. mutans were genotyped by arbitrarily primed polymerase chain reaction using OPA2 primer. One isolate from each genotype was tested for its acid susceptibility and its ability to form a biofilm. Results: Fifty‐one distinct genotypes were determined, one to three genotypes in each oral sample. A single genotype was detected in seven children, whereas the remaining 14 children exhibited two to seven genotypes. There were no significant differences in the number of genotypes detected in caries‐free and caries‐active children. No correlation was observed between the number of genotypes and the mutans streptococci salivary levels. Five of the six high biofilm‐forming genotypes were obtained from caries‐active children, although the differences in biofilm formation between isolates from caries‐free and caries‐active children were not statistically significant. Genotypes with low susceptibility to acid challenge were statistically more frequent among isolates from caries‐active children than among those from caries‐free children. Conclusion: The present data suggested that there were differences in the distribution of genotypes of S. mutans according to the oral site and that S. mutans populations differ in their acid susceptibility and ability to form biofilms, factors allowing their colonization of sucrose‐rich environments.     

Catechol-O-methyltransferase (COMT) genotypes and working memory: associations with differing cognitive operations.

BACKGROUND: Catechol-O-methyltransferase (COMT) is a strong candidate gene for schizophrenia and cognitive functions disrupted in this disorder. This report examines the relation of COMT genotypes to performance on a battery of working memory tests differing in the cognitive operations to be performed on the material. METHODS: A large sample of 402 healthy adults were tested on four working memory tests: Spatial Delayed Response (SDR), Word Serial Position Test (WSPT), N-back, and Letter-Number Sequencing. A subsample (n = 246) was tested on the Wisconsin Card Sorting Test (WCST). A saliva swab was used to obtain DNA from all participants. RESULTS: Letter-Number Sequencing, which requires both storage and manipulation of information, was the only working memory test that showed expected differences among COMT genotypes, with the met/met group showing the best performance and the val/val group the poorest performance. As in previous studies, the met/met group also performed better than the val/val group on the WCST. CONCLUSIONS: COMT genotypes were not associated with performance on tests measuring simple storage, maintenance of temporal order or updating of information in working memory. Genotype differences in Letter-Number Sequencing and WCST suggest that higher-order components of processing (e.g., mental manipulation) are more closely related to this gene.     

Evidence for an association of TP53 codon 72 polymorphism with breast cancer risk

BACKGROUND: A common Arg/Pro polymorphism at codon 72 of the TP53 gene has been investigated as a risk factor for cancer in different populations. So far, the results have been controversial. Our purpose was to investigate the association of this polymorphism with breast carcinoma in women from Southern Brazil, a high-risk area for breast cancer. METHODS: Blood samples collected from 118 women with primary breast carcinoma and from 202 female blood donors were analyzed through polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. RESULTS: The relative frequency of each allele was 0.75 for Arg and 0.25 for Pro in patients with cancer, and 0.62 for Arg and 0.38 for Pro in normal controls (P < 0.001). The Arg/Arg genotype was significantly associated with an increased risk for breast cancer (OR 2.9; 95% CI 1.43-3.6; P < 0.002). No correlation between the genotype distribution and specific prognostic predictors for the disease outcome was observed. DISCUSSION: TP53 codon 72 polymorphism might be implicated in breast carcinogenesis, with the Arg/Arg genotype being associated with an increased susceptibility for this malignancy.