Molecular epidemiology identifies HIV transmission networks associated with younger age and heterosexual exposure among Korean individuals.
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ABSTRACT:
SUBMITTER: Chin BS
PROVIDER: S-EPMC4969179 | biostudies-literature | 2016 Oct
REPOSITORIES: biostudies-literature
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Project description:Most human immunodeficiency virus type 1 (HIV-1) transmissions in sub-Saharan Africa are believed to occur between married adults who are discordant for their HIV-1 infection status; however, no studies to date have investigated the molecular epidemiology of such transmission events. Here we report the genetic characterization of HIV-1 strains from 149 transmission pairs that were identified prospectively in a cohort of discordant couples in Lusaka, Zambia. Subgenomic gag, gp120, gp41, and/or long terminal repeat regions were amplified by PCR analysis of uncultured blood samples from both partners and sequenced without interim cloning. Pairwise genetic distances were calculated for the regions analyzed and compared to those of subtype-specific reference sequences as well as local controls. Sequence relationships were also examined by phylogenetic tree analysis. By these approaches, epidemiological linkage was established for the majority of transmission pairs. Viruses from 129 of the 149 couples (87%) were very closely related and clustered together in phylogenetic trees in a statistically highly significant manner. In contrast, viruses from 20 of the 149 couples (13%) were only distantly related in two independent genomic regions, thus ruling out transmission between the two partners. The great majority (95%) of transmitted viruses were of subtype C origin, although representatives of subtypes A, D, G, and J were also identified. There was no evidence for extensive transmission networks within the cohort, although two phylogenetic subclusters of viruses infecting two couples each were identified. Taken together, these data indicate that molecular epidemiological analyses of presumed transmission pairs are both feasible and required to determine behavioral, virological, and immunological correlates of heterosexual transmission in sub-Saharan Africa with a high level of accuracy.
| S-EPMC135722 | biostudies-literature
Project description:BackgroundA large number of HIV-1 infections in Africa occur in married couples. The predominant direction of intracouple transmission and the principal external origins of infection remain important issues of debate.MethodsWe investigated HIV-1 transmission in 46 HIV-1 concordant positive couples from Dakar, Senegal. Intracouple transmission was confirmed by maximum-likelihood phylogenetic analysis and pairwise distance comparisons of HIV-1 env gp41 sequences from both partners. Standardized interview data were used to deduce the direction as well as the external sources of the intracouple transmissions.ResultsConservative molecular analyses showed linked viruses in 34 (74%) couples, unlinked viruses in 6 (13%) couples, and indeterminate results for 6 (13%) couples. The interview data corresponded completely with the molecular analyses: all linked couples reported internal transmission and all unlinked couples reported external sources of infection. The majority of linked couples (93%) reported the husband as internal source of infection. These husbands most frequently (82%) reported an occasional sexual relationship as external source of infection. Pairwise comparisons of the CD4 count, antiretroviral therapy status, and the proportion of gp41 ambiguous base pairs within transmission pairs correlated with the reported order of infection events.ConclusionsIn this suburban Senegalese population, a majority of HIV-1 concordant couples showed linked HIV-1 transmission with the husband as likely index partner. Our data emphasize the risk of married women for acquiring HIV-1 as a result of the occasional sexual relationships of their husbands.
| S-EPMC3355130 | biostudies-literature
Project description:We examined the transmission of human papillomavirus (HPV) in 25 heterosexual, monogamous couples (25 men, 25 women), followed up over an average of 7.5 months. A total of 53 heterosexual transmission events were observed among 16 couples (14 male-to-female and 39 female-to male). Sexual transmission involved 13 different oncogenic and nononcogenic HPV types; 8% were vaccine-covered types transmitted between partners. The overall rate of HPV transmission from the penis to the cervix was 4.9/100 person-months, which was substantially lower than that from the cervix to the penis (17.4/100 person-months). Transmission between the hands and genitals, as well as apparent self-inoculation events (primarily in men), were also observed. Couples who transmitted HPV were more sexually active and used condoms less frequently. These results have implications for HPV prevention and control strategies, including the targeting of prophylactic vaccines.
| S-EPMC2600292 | biostudies-literature
Project description:Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked transmission pairs, the amino acid sequences encoded by non-envelope genes of viruses in both partners and demonstrate a selection bias for transmission of residues that are predicted to confer increased in vivo fitness on viruses in the newly infected, immunologically naïve recipient. Although tempered by transmission risk factors, such as donor viral load, genital inflammation, and recipient gender, this selection bias provides an overall transmission advantage for viral quasispecies that are dominated by viruses with high in vivo fitness. Thus, preventative or therapeutic approaches that even marginally reduce viral fitness may lower the overall transmission rates and offer long-term benefits even upon successful transmission.
| S-EPMC4289910 | biostudies-literature
Project description: Not available
| S-EPMC1122131 | biostudies-literature
Project description:BackgroundGenovar distributions of Chlamydia trachomatis based on ompA typing differ between men who have sex with men (MSM) and heterosexuals. We investigated clonal relationships using a high resolution typing method to characterize C. trachomatis types in these two risk groups.MethodsC. trachomatis positive samples were collected at the STI outpatient clinic in Amsterdam between 2008 and 2010 and genotyped by multilocus sequence typing. Clusters were assigned using minimum spanning trees and these were combined with epidemiological data of the hosts.ResultsWe typed 526 C. trachomatis positive samples: 270 from MSM and 256 from heterosexuals. Eight clusters, containing 10-128 samples were identified of which 4 consisted of samples from MSM (90%-100%), with genovars D, G, J, and L2b. The other 4 clusters consisted mainly of samples from heterosexuals (87%-100%) with genovars D, E, F, I, and J. Genetic diversity was much lower in the MSM clusters than in heterosexual clusters. Significant differences in number of sexual partners and HIV-serostatus were observed for MSM-associated clusters.ConclusionsC. trachomatis transmission patterns among MSM and heterosexuals were largely distinct. We hypothesize that these differences are due to sexual host behavior, but bacterial factors may play a role as well.
| S-EPMC3547048 | biostudies-literature
Project description:Background: Glioblastomas are the most common primary brain tumour in adults. While the prognosis for patients is poor, gene expression profiling has detected signatures that can sub-classify GBMs relative to histopathology and clinical variables. One category of GBM defined by a gene expression signature is termed ProNeural (PN), and has substantially longer patient survival relative to other gene expression-based subtypes of GBMs. Age of onset is a major predictor of the length of patient survival where younger patients survive longer than older patients. The reason for this survival advantage has not been clear. We collected 267 GBM CEL files and normalized them relative to other microarrays of the same Affymetrix platform. 377 probesets on U133A and U133 Plus 2.0 arrays were used in a gene voting strategy with 177 probesets of matching genes on older U95Av2 arrays. Kaplan-Meier curves and Cox proportional hazard analyses were applied in distinguishing survival differences between expression subtypes and age. Results: Here we collected 267 glioblastomas and explore the relationship between gene expression subtype, age at diagnosis, and survival. This meta-analysis of published data in addition to new data confirms the existence of four distinct GBM expression-signatures. Further, patients with PN subtype GBMs had longer survival, as expected. However, the age of the patient at diagnosis is not predictive of survival time when controlled for the PN subtype. Conclusions: The survival benefit of younger age is nullified when patients are stratified by gene expression group. Thus, the main cause of the age effect in GBMs is the more frequent occurrence of PN GBMs in younger patients relative to older patients. Experiment Overall Design: Clinical data including histopathology, age, sex, and survival time from diagnosis were retrieved from 181 glioblastomas which have been reported within previous studies between 2003 and 2006 and for which CEL files (Affymetrix, Santa Clara, CA) were available from the authors. In addition, we collected 86 new patient-unique tumour biopsies from the UCLA Neuro-oncology Program (n = 55) and the Barrow Neurological Institute (n = 31) for a grand total of 267 glioblastomas. Newly acquired tumours were collected through institutional review board approved protocols and assigned WHO grades at UCLA Neuropathology or Barrow Neuropathology by PSM. Time of survival (days), sex, and, age were collected where available. Patient age at the time of diagnosis was available for 239 patients and ranged from 18 to 86 years. Sex of the individual was available for those 239 patients (151 males and 88 females). There were no technical replicates. There were no control or reference samples. No dye swap due to single channel array platforms.
2008-10-26 | E-GEOD-13041 | biostudies-arrayexpress
Project description:Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18-53, 54-64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p54-63 = 1.50x10-9 , OR54-63 = 1.28, 95%CI54-63 = 1.18-1.39; p64+ = 2.14x10-11 , OR64+ = 1.32, 95%CI64+ = 1.21-1.43] and rs11979158 [p54-63 = 6.13x10-8 , OR54-63 = 1.35, 95%CI54-63 = 1.21-1.50; p64+ = 2.18x10-10 , OR64+ = 1.42, 95%CI64+ = 1.27-1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18-53 (p18-53 = 9.30 × 10-11 , OR18-53 = 1.76, 95%CI18-53 = 1.49-2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of 'LGG'-like tumor characteristics in GBM samples in those 18-53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54-63] and 0.8% [64+] (p = 0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18-53 suggests that more younger individuals may present initially with 'secondary glioblastoma.'
| S-EPMC6205887 | biostudies-literature
Project description:Chronological age (CA) predicts health status but its impact on health varies with anthropometry, socioeconomic status (SES), and lifestyle behaviors. Biological age (BA) is, therefore, considered a more precise predictor of health status. We aimed to develop a BA prediction model from self-assessed risk factors and validate it as an indicator for predicting the risk of chronic disease. A total of 101,980 healthy participants from the Korean Genome and Epidemiology Study were included in this study. BA was computed based on body measurements, SES, lifestyle behaviors, and presence of comorbidities using elastic net regression analysis. The effects of BA on diabetes mellitus (DM), hypertension (HT), combination of DM and HT, and chronic kidney disease were analyzed using Cox proportional hazards regression. A younger BA was associated with a lower risk of DM (HR = 0.63, 95% CI: 0.55-0.72), hypertension (HR = 0.74, 95% CI: 0.68-0.81), and combination of DM and HT (HR = 0.65, 95% CI: 0.47-0.91). The largest risk of disease was seen in those with a BA higher than their CA. A consistent association was also observed within the 5-year follow-up. BA, therefore, is an effective tool for detecting high-risk groups and preventing further risk of chronic diseases through individual and population-level interventions.
| S-EPMC8955355 | biostudies-literature
Project description:Background: Glioblastomas are the most common primary brain tumour in adults. While the prognosis for patients is poor, gene expression profiling has detected signatures that can sub-classify GBMs relative to histopathology and clinical variables. One category of GBM defined by a gene expression signature is termed ProNeural (PN), and has substantially longer patient survival relative to other gene expression-based subtypes of GBMs. Age of onset is a major predictor of the length of patient survival where younger patients survive longer than older patients. The reason for this survival advantage has not been clear. We collected 267 GBM CEL files and normalized them relative to other microarrays of the same Affymetrix platform. 377 probesets on U133A and U133 Plus 2.0 arrays were used in a gene voting strategy with 177 probesets of matching genes on older U95Av2 arrays. Kaplan-Meier curves and Cox proportional hazard analyses were applied in distinguishing survival differences between expression subtypes and age. Results: Here we collected 267 glioblastomas and explore the relationship between gene expression subtype, age at diagnosis, and survival. This meta-analysis of published data in addition to new data confirms the existence of four distinct GBM expression-signatures. Further, patients with PN subtype GBMs had longer survival, as expected. However, the age of the patient at diagnosis is not predictive of survival time when controlled for the PN subtype. Conclusions: The survival benefit of younger age is nullified when patients are stratified by gene expression group. Thus, the main cause of the age effect in GBMs is the more frequent occurrence of PN GBMs in younger patients relative to older patients. Keywords: Gene expression profiling, GBM, glioblastoma, survival, MGMT, VEGFA, EGFR, Temozolomide, Affymetrix
2008-10-10 | GSE13041 | GEO