Loredana Covolo

IL28B polymorphisms, IP-10 and viral load predict virological response to therapy in chronic hepatitis C.

Aliment Pharmacol Ther 2011; 33: 1162–1172

Bladder cancer, GSTs, NAT1, NAT2, SULT1A1, XRCC1, XRCC3, XPD genetic polymorphisms and coffee consumption: a case–control study

The aim of the study was to investigate NAT1, NAT2, GSTM1, GSTT1, GSTP1, SULT1A1, XRCC1, XRCC3 and XPD genetic polymorphisms, coffee consumption and risk of bladder cancer (BC) through a hospital-based case–control study. The study population included 197 incident BC cases and 211 controls. The association between genetic polymorphisms, coffee drinking and BC risk was assessed by logistic regression taking into account age, education, tobacco smoking and occupational exposures to polycyclic aromatic hydrocarbons and aromatic amines. No association was found between the genetic polymorphisms investigated and BC risk according to coffee consumption apart of a significant increased BC risk among GSTP1 105-114 Val carriers heavy coffee drinkers (>3 cups/day) (OR 3.18, 95%CI 1.06–9.55). In conclusion our findings suggest a very limited role, if any, of genetic polymorphisms investigated in modulating the BC risk in coffee drinkers.

ATP13A2 (PARK9) polymorphisms influence the neurotoxic effects of manganese.

INTRODUCTION A higher prevalence of individuals affected by Parkinsonism was found in Valcamonica, Italy. This may be related to ferro-alloy smelters in the area, releasing manganese (Mn) in the air, soil and water for about a century. There exists individual susceptibility for Mn neurotoxicity. AIM To analyse how polymorphism in genes regulating Mn metabolism and toxicity can modify neurophysiological effects of Mn exposure. MATERIALS AND METHODS Elderly (N=255) and adolescents (N=311) from Northern Italy were examined for neuromotor and olfactory functions. Exposure to Mn was assessed in blood and urine by atomic absorption spectroscopy and in soil by a portable instrument based on X-Ray fluorescence technology. Polymorphisms in the Parkinson-related gene ATPase type 13A2 (ATP13A2, also called PARK9: rs3738815, rs2076602, rs4920608, rs2871776 and rs2076600), and in the secretory pathway Ca(2+)/Mn(2+) ATPase isoform 1 gene (SPCA1: rs218498, rs3773814 and rs2669858) were analysed by TaqMan probes. RESULTS For both adolescents and elderly, negative correlations between Mn in soil and motor coordination (R(s)=-0.20, p<0.001; R(s)=-0.13, p=0.05, respectively) were demonstrated. Also among adolescents, negative correlations were seen between Mn in soil with odor identification (R(s)=-0.17, p<0.01). No associations were seen for Mn in blood or urine. ATP13A2 polymorphisms rs4920608 and rs2871776 significantly modified the effects of Mn exposure on impaired motor coordination in elderly (p for interaction=0.029, p=0.041, respectively), also after adjustments for age and gender. The rs2871776 altered a binding site for transcription factor insulinoma-associated 1. CONCLUSIONS ATP13A2 variation may be a risk marker for neurotoxic effects of Mn in humans.

Internet-Based Direct-to-Consumer Genetic Testing: A Systematic Review.

Background Direct-to-consumer genetic tests (DTC-GT) are easily purchased through the Internet, independent of a physician referral or approval for testing, allowing the retrieval of genetic information outside the clinical context. There is a broad debate about the testing validity, their impact on individuals, and what people know and perceive about them. Objective The aim of this review was to collect evidence on DTC-GT from a comprehensive perspective that unravels the complexity of the phenomenon. Methods A systematic search was carried out through PubMed, Web of Knowledge, and Embase, in addition to Google Scholar according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist with the key term “Direct-to-consumer genetic test.” Results In the final sample, 118 articles were identified. Articles were summarized in five categories according to their focus on (1) knowledge of, attitude toward use of, and perception of DTC-GT (n=37), (2) the impact of genetic risk information on users (n=37), (3) the opinion of health professionals (n=20), (4) the content of websites selling DTC-GT (n=16), and (5) the scientific evidence and clinical utility of the tests (n=14). Most of the articles analyzed the attitude, knowledge, and perception of DTC-GT, highlighting an interest in using DTC-GT, along with the need for a health care professional to help interpret the results. The articles investigating the content analysis of the websites selling these tests are in agreement that the information provided by the companies about genetic testing is not completely comprehensive for the consumer. Given that risk information can modify consumers’ health behavior, there are surprisingly few studies carried out on actual consumers and they do not confirm the overall concerns on the possible impact of DTC-GT. Data from studies that investigate the quality of the tests offered confirm that they are not informative, have little predictive power, and do not measure genetic risk appropriately. Conclusions The impact of DTC-GT on consumers’ health perceptions and behaviors is an emerging concern. However, negative effects on consumers or health benefits have yet to be observed. Nevertheless, since the online market of DTC-GT is expected to grow, it is important to remain aware of a possible impact.

Role of β1- and α2c-adrenergic receptor polymorphisms and their combination in heart failure: A case-control study☆

Adrenergic activation has a central role in the development of HF. The function of the β1‐ and the α2C‐adrenergic receptors is influenced by gene polymorphisms: the β1Arg389 variant is associated with increased β1‐receptor sensitivity and the α2C‐receptor Del322–325 variant is associated with decreased α2C receptor function and increased norepinephrine release. We hypothesised that these polymorphisms could influence the prevalence of heart failure.

The homeostasis model assessment of the insulin resistance score is not predictive of a sustained virological response in chronic hepatitis C patients

Objectives: To investigate the independent association between the homeostasis model assessment of the insulin resistance (HOMA‐IR) score and rapid virological response (RVR) and sustained virological response (SVR) in chronic hepatitis C (CHC).

Etiology of hepatocellular carcinoma influences clinical and pathologic features but not patient survival.

OBJECTIVES:We investigated the relation between hepatocellular carcinoma (HCC) etiology and biological and clinical parameters indicative of severity of liver disease and/or tumor characteristics and patient survival.METHODS:We prospectively recruited 384 patients (82.3% male) with first diagnosis of HCC from 1995 to 1998 in Brescia, Italy. Etiology was assessed by interviewing patients regarding their history of alcohol intake and by testing sera for hepatitis B surface antigen and anti-hepatitis C virus (HCV) antibodies and HCV RNA.RESULTS:Heavy alcohol intake (>60 g of ethanol per day for at least 1 decade) was found in 33.1% of cases, hepatitis B virus (HBV) infection in 9.4%, HCV in 19.8%, hemochromatosis in 1.3%, alcohol and HBV in 12.0%, alcohol and HCV in 16.1%, HBV and HCV in 3.1%, and no factor in 5.2%. Patients with HBV infection with or without heavy alcohol intake were significantly younger than the others (61.7 vs 64.7 yr, p < 0.001). The proportion of males was significantly higher in patients with heavy alcohol intake alone than in the other patient groups (93.7% vs 77.3%, p < 0.001). Among patients with HCV infection with or without heavy alcohol intake, fewer patients had maximum tumor diameter > 5 cm than the others (12% vs 29.1%, p < 0.001). Eighty patients (20.8%) were alive at the end of follow-up (median survival, 17.7 months), and no differences were observed in survival rates by HCC risk factor.CONCLUSIONS:Although some differences were observed in severity of liver disease or tumor characteristics according to etiology, patient survival was not influenced by HCC etiology.

N-Acetyltransferase-2, glutathione S-transferase M1 and T1 genetic polymorphisms, cigarette smoking and hepatocellular carcinoma: a case-control study.

Our aim was to evaluate the role of N‐acetyltransferase (NAT2) and glutathione S‐transferase M1 and T1 (GSTM1 and GSTT1) polymorphisms in hepatocellular carcinoma (HCC) according to cigarette smoking, taking into account hepatitis B (HBV) and C (HCV) viral infection as well as alcohol consumption. A hospital‐based case‐control study was conducted in 2 areas of north Italy. Cases (n = 200) were patients hospitalized for HCC, and controls (n = 400) were patients admitted for reasons other than liver disease, neoplasms and tobacco‐ and alcohol‐related diseases. Genotypes were determined using PCR and the PCR/restriction fragment length polymorphism–based method. The putative risk genotypes NAT2 slow acetylator, GSTM1 null and GSTT1 null were not associated with HCC (OR = 1.3, 95% CI 0.8–2.0; OR = 1.0, 95% CI 0.6–1.5; OR = 0.8, 95% CI 0.4–1.4, respectively). Although not statistically significant, an increase in HCC risk was observed among light smokers (1–20 pack‐years) carrying GSTT1 null (OR = 1.7, 95% CI 0.6–4.7) and NAT2 slow acetylator (OR = 1.3, 95% CI 0.6–3.0) genotypes. In conclusion, there was no evidence for a gene–environment interaction in HCC risk for GSTM1, GSTT1 and NAT2 genotypes.

Effectiveness and Tolerability of Combination Treatment of Chronic Hepatitis C in Illicit Drug Users: Meta-Analysis of Prospective Studies

BACKGROUND Hepatitis C virus (HCV) infection is a global health problem. In Western countries, illicit drug users (IDUs) constitute the largest proportion of HCV patients. International guidelines no longer regard ongoing illicit drug use as a contraindication to antiviral therapy for chronic hepatitis C (CHC). Nonetheless, in clinical practice, few IDUs have access to HCV treatment, likely because many physicians believe these patients will have poor adherence or a lack of treatment efficacy. OBJECTIVE The aim of this study was to assess effectiveness and tolerability of combination treatment with ribavirin plus recombinant or pegylated interferon-α in the treatment of CHC in IDUs. METHODS MEDLINE, EMBASE, and the Cochrane Library were searched for relevant studies published in English between 2000 and December 2008. The following terms were searched: chronic hepatitis C, interferons, antiviral agents, methadone, and substance-related disorders. Full-text articles and abstracts were searched using predefined criteria. A manual search of abstracts from 8 international meetings of hepatologists was also conducted. Only prospective studies with a sample size >15 and a homogeneous treatment schedule were included. Articles were extracted independently by 2 of the authors using an electronic standardized form including study quality indicators. RESULTS Sixteen prospective studies were included, and data from a cohort of 953 IDUs were analyzed. The estimated overall sustained virologic response (SVR) and dropout (DO) rates in IDUs were 52% (95% CI, 44%-60%) and 26% (18%-35%, 95% CI), respectively. The rate of psychiatric severe adverse events (SAEs) that led to treatment discontinuation was 2% (95% CI, 1%-3%). These prevalences were not significantly different from those reported in registration trials of treatment of CHC that excluded IDUs from the study population (SVR, 50% [95% CI, 39%-61%]; DO, 26% [95% CI, 12%-41%]; and psychiatric SAEs, 2% [95% CI, 0%-6%]). By subgroup analysis, active ongoing drug use negatively affected the rate of treatment success (39% [95% CI, 30%-49%] vs 55% [95% CI, 45%-64%]; P = 0.02). CONCLUSION Based on data from 16 prospective clinical studies of CHC treatment in IDUs published in the past 10 years, findings on effectiveness and tolerability are comparable to those in the general population.

The novel ss469415590 variant predicts virological response to therapy in patients with chronic hepatitis C virus type 1 infection

A novel dinucleotide variant TT/∆G (ss469415590) has been associated with hepatitis C virus clearance.