Association of interleukin-28B rs12979860 and rs8099917 polymorphisms with sustained viral response in hepatitis C virus genotype 1 and 3 infected patients from the Indian subcontinent.

BACKGROUND: Polymorphisms of the IL28B gene (rs12979860 and rs8099917) have been shown to impact treatment responses in hepatitis C virus (HCV) infected patients. The association of these polymorphisms with sustained viral response (SVR) has been studied in HCV genotype 3 infected patients in India, but not in genotype 1. OBJECTIVES: This study aimed to determine the association of IL28B gene polymorphisms and other host and viral factors with treatment response in patients with HCV genotype 1 and 3 infection. MATERIALS AND METHODS: DNA from 42 HCV-infected patients on antiviral therapy was analysed for the IL28B polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Bidirectional sequencing was performed on a subset of samples for verification of PCR-RFLP results. Information on age, weight, height, diabetic status, pre-treatment viral load and alanine aminotransferase (ALT) levels was obtained from clinical records. The IL28B genotypes and the other factors were analysed for their association with SVR. RESULTS: The frequency distribution of rs12979860 CC/CT/TT genotypes was found to be 66.7%, 26.2% and 7.1%, respectively. For rs8099917 genotype, the TT/GT/GG distribution was 73.8%, 21.4% and 4.8%, respectively. SVR was seen in 61.9% of cases (55.6% in genotype 1 and 62.5% in genotype 3). CC genotype at rs12979860 and TT genotype at rs8099917 were significantly higher in responders (P = 0.013 and 0.042, respectively). Lower baseline ALT and rapid viral response were also found to be associated with SVR. On logistic regression analysis, CC genotype at rs12979860 emerged as the most powerful predictor of treatment response. CONCLUSION: IL28B polymorphisms are strong predictors of SVR in patients from the Indian subcontinent infected with HCV genotype 3 and genotype 1.

Prevalence of non-responsiveness to an indigenous recombinant hepatitis B vaccine: a study among South Indian health care workers in a tertiary hospital.

BACKGROUND AND AIM: Health care workers (HCW) are at higher risk of contracting HBV infection. Non-response to HBV vaccine is one of the major impediments to prevent healthcare associated HBV infection (HAHI). We estimated the prevalence of non-responsiveness to initial 3-dose regimen of an indigenous recombinant HBV vaccine (GeneVac-B) among South Indian HCWs and typed the HLA in non-responders. STUDY DESIGN AND METHOD: Of the 778 subjects screened over 1 year, 454 completed all three doses of the hepatitis B vaccination. Anti-HBs titers were estimated by microparticle enzyme immunoassay AxSYM AUSAB, (Abbott, Germany). HLA typing was done using SSP-PCR assay AllSet+™ Gold SSP (Invitrogen, USA). RESULTS: The overall seroconversion rate (anti-HBs>10 mIU/mL) was 98.89% wherein 90.8% had titers>1000mIU/mL, 7.6% had titers 100-1000mIU/mL, 0.43% had titers<100 mIU/mL and 1.1% were non-responsive (<10 mIU/mL) to the initial 3-dose regimen. Antibody titers<1000 mIU/mL were significantly associated with the highest quartile of body mass index (BMI) (P<0.001). We found no significant difference in seroprotection rate between gender (P=0.088). There was no difference in seroprotection rates among various ethnic groups (P=0.62). Subjects who were non-responsive in our study had at least one HLA allele earlier known to be associated with non-responsiveness to the vaccine. CONCLUSION: Our findings suggest that non-response to HBV vaccine is not a major impediment to prevent HAHI. Robust seroprotection rates can be achieved using this indigenous HBV vaccine. However, gender and BMI might influence the level of anti-HBs titers. We recommend the use of this cost effective HBV vaccine as well as postvaccination anti-HBs testing to prevent HAHI among HCWs.

Human herpes virus-8 infections among subjects with human immunodeficiency virus infection and normal healthy individuals in India.

Human herpes virus-8 (HHV-8) is etiologically associated with Kaposi's sarcoma. There is insufficient information on the epidemiology of HHV-8 infection from India. Blood samples from 87 human immunodeficiency virus (HIV)-infected individuals and 84 normal healthy blood donors were tested for the HHV-8 IgG antibodies. Further, a total of 309 whole blood samples from treatment-naïve HIV-1-infected individuals and from 70 normal healthy individuals were also collected and tested for HHV-8 DNA. The seroprevalence of HHV-8 was 4.7% in the South Indian population. There was no significant difference in the seroprevalence of HHV-8 in the HIV-infected and uninfected patients. None of the 379 samples tested were positive for HHV-8 DNA. Our study revealed a very low exposure of the South Indian patient population to HHV-8 and multicentric epidemiological studies are needed to understand the prevalence of HHV-8 in different regions of India and to confirm any gender-specific differences in seroprevalence.

Association of HLA and TNF polymorphisms with the outcome of HBV infection in the South Indian population.

The role of host genetic factors in the pathogenesis and outcome of hepatitis B virus (HBV) infection is not well known. We assessed the association of HLA and TNF (rs361525, rs1800629, rs1799724, rs1800630 and rs1799964) polymorphisms with HBV outcome in the South Indian population. Association of HLA polymorphism was analyzed in 90 individuals from each group, that is, spontaneous recovery (SR) and chronic-HBV (C-HBV) infection. The role of TNF polymorphisms was evaluated in 150 subjects with SR and 137 patients with C-HBV infection. After adjusting for age and sex, HLA-DRB1*07:01 was strongly associated with chronicity (corrected P-value (pc) <0.005, odds ratio (OR) 3.76, 95% confidence interval (CI) 1.84-7.68). The rs1800630 genotype was associated with HBV outcome in codominant (pc<0.01, OR=1.99, 95% CI 1.30-3.05) and dominant (pc<0.01, OR=2.28, 95% CI 1.35-3.84) analyzing models after adjusting for age and sex. Similarly, the rs1799964 genotype was associated with HBV outcome in codominant (pc=0.01, OR=1.57, 95% CI 1.09-2.27) and dominant (pc<0.01, OR=2.21, 95% CI 1.27-3.83) analyzing models. Haplotype analysis (rs1799964/rs1800630/rs1799724/rs1800629/rs361525) revealed that the CACGG haplotype was strongly associated with C-HBV infection (P=0.0004). Our study suggests that inheritance of HLA and TNF polymorphisms might explain the outcome of HBV infection in the South Indian population.

Association of mannose-binding lectin polymorphisms and HBV outcome in a South Indian population.

Mannose binding lectin (MBL) is an important innate immune system pattern recognition molecule. The MBL gene polymorphisms are reported to play a crucial role in outcome of hepatitis B virus (HBV) infection. In this study, we ascertained the association of MBL genotypes with HBV outcome in a South Indian population. The MBL gene polymorphisms at codons 52, 54 and 57 of exon I, and promoter polymorphisms at -221 were typed by polymerase chain reaction-sequence specific primer in spontaneously recovered and in chronic HBV group. The allele frequency of codon 52 'C' was significantly higher in chronic HBV group than in the recovered group (98.5% vs. 93.6%; P = 0.003) and codon 52 'T' was significantly higher in recovered group than in the chronic group (6.4% vs. 1.5%; P = 0.003). In multivariate analysis, after adjusting for age, sex and state of origin, codon 52 'CC' and 'CT' genotypes were significantly associated with chronicity and recovery respectively [odds ratio (OR), 0.25; 95% confidence interval (CI), 0.08-0.80, P = 0.02] in co-dominant analyzing models. This was re-affirmed in analysis performed exclusively on Tamil Nadu subjects (OR, 0.23; 95% CI, 0.06-0.93, P = 0.039). The frequency of low/none haplotype (XY/O) was significantly higher in recovered group than in chronic group (15.6% vs 7.5%) and associated with spontaneous recovery (OR, 2.28; 95% CI, 1.04-4.99, P = 0.035). Our results provide preliminary evidence that inheritance of codon 52 genotypes and XY/O haplotype associated with low MBL level substantially determine the outcome of HBV infection in a sympatrically isolated South Indian population.

Expression of multiple forms of ferredoxin NADP+ oxidoreductase in wheat leaves.

In higher plants there are two forms of ferredoxin NADP(+) oxidoreductase (FNR), a photosynthetic pFNR primarily required for the photoreduction of NADP(+), and a heterotrophic hFNR which generates reduced ferredoxin by utilizing electrons from NADPH produced during carbohydrate oxidation. The aim of this study was to investigate the presence of multiple forms of FNR in wheat leaves and the capacity of FNR isoforms to respond to changes in reductant demand through varied expression and N-terminal processing. Two forms of pFNR mRNA (pFNRI and pFNRII) were expressed in a similar pattern along the 12 cm developing primary wheat leaf, with the highest levels observed in plants grown continuously in the dark in the presence (pFNRI) or absence (pFNRII) of nitrate respectively. pFNR protein increased from the leaf base to tip. hFNR mRNA and protein was in the basal part of the leaf in plants grown in the presence of nitrate. FNR activity in plants grown in a light/dark cycle without nitrate was mainly due to pFNR, whilst hFNR contributed significantly in nitrate-fed plants. The potential role of distinct forms of FNR in meeting the changing metabolic capacity and reductant demands along the linear gradient of developing cells of the leaf are discussed. Furthermore, evidence for alternative N-terminal cleavage sites of pFNR acting as a means of discriminating between ferredoxins and the implications of this in providing a more effective flow of electrons through a particular pathway in vivo is considered.

Ideals, perceptions, and evaluations in early relationship development.

This research examined partner and relationship perceptions and ideal standards in 100 individuals over time, from the 1st to the 12th month of their dating relationships. As expected, the results revealed that (a) individuals evaluated their relationships on both distinct evaluative components and global evaluative dimensions, (b) higher ideal-perception consistency was associated with higher perceived quality of relationships and partners, (c) more positive perceptions of partners and relationships at earlier points in time were associated with more importance being placed on relevant ideals over time but not vice versa, and (d) higher levels of ideal-perception consistency predicted lower rates of relationship dissolution but were mediated through perceptions of relationship quality. These results support the ideal standards model (Fletcher & Simpson, in press).

Ideals in intimate relationships.

This research examined lay relationship and partner ideals in romantic relationships from both a social-cognitive and an evolutionary perspective. Studies 1 and 2 revealed that the qualities of an ideal partner were represented by 3 factors (partner warmth-trustworthiness, vitality-attractiveness, and status-resources), whereas the qualities of an ideal relationship were represented by 2 factors (relationship intimacy-loyalty and passion). A confirmatory factor analysis in Study 3 replicated these factor structures but found considerable overlap across the partner and relationship dimensions. Studies 4 and 5 produced convergent and discriminant validity evidence for all 5 factors. Study 6 indicated that the higher the consistency between the ideals and related assessments of the current partner and relationship, the more positively the current relationship was evaluated.

Love, hate, anger, and jealousy in close relationships: a prototype and cognitive appraisal analysis.

The aim of this research was to make a prototype and cognitive appraisal analysis of 4 emotions within marriage. In Study 1, 160 Ss recalled and wrote about a partner-related love, hate, anger, or jealousy incident. Distinct prototypes and appraisal patterns were obtained. In Study 2, 80 Ss wrote accounts of hypothetical love, hate, anger, and jealousy events in marriage. The results suggested both recalled and hypothetical accounts were derived from the same knowledge structures. In Study 3, Ss matched emotions to events described with varying amounts of prototypical and appraisal information, derived from Study 1. Adding such information significantly increased emotion-matching accuracy over the event-description-only condition. The results are discussed in relation to prototype and cognitive appraisal theories of emotion in close relationships.

The role of attributions in the development of dating relationships.

In this study, we examine the role of attributions in the context of dating relationships. A large sample completed a questionnaire comprising structured ratings and a free-response relationship description. As expected, cognitive or attributional activity was more frequent within relationships when they were in the early stages, when important choice points or changes were occurring, and when the relationships were perceived as unstable. Also as predicted, subjects who reported higher relationship happiness, commitment, and love for their partners tended to describe the relationship in more interpersonal terms, to rate the causal inputs of the partners as equal, and to attribute lower external attributions for relationship maintenance. Finally, some evidence was obtained that attributions for relationship maintenance are causally related to relationship happiness over a 2-month period. The results are discussed in terms of the relationship between cognitive processing and the development of dating relationships.