Dataset Information

A preliminary assessment of Toll-like receptor and ?-defensin gene polymorphisms in Papua New Guinea - what does it mean for HIV/AIDS?

ABSTRACT: Polymorphisms in Toll-like receptor (TLR) and human ?-defensin (hBD, encoded by DEFB) genes have been evaluated for their associations with HIV infection and disease outcomes. Those studies, conducted in various populations under a variety of study designs, generally revealed that specific single nucleotide polymorphisms (SNPs) in TLR1, 2, 3, 4, 6, 7, 8, and 9 genes, and copy number variation (CNV) in DEFB4 (encoding hBD-2), DEFB103A (encoding hBD-3), and DEFB104A (encoding hBD-4) genes are among potential genetic factors that can affect susceptibility to HIV infection and/or disease progression. The information regarding their prevalence in Papua New Guinea (PNG) is very limited for TLR SNPs, and not available for DEFB CNV. The present study provides a preliminary assessment of these genetic polymorphisms in samples collected from the Wosera (East Sepik Province, n = 29) and Liksul (Madang Province, n = 23) areas. Wosera samples were analyzed for a total of 41 SNPs in 8 TLR genes (TLR1, 2, 3, 4, 6, 7, 8, and 9), and both sample sets were analyzed for CNV in DEFB4/103A/104A genes. A number of TLR SNPs were not detected, and many other SNPs were present at low frequencies (minor allele frequencies ?0.05) in the Wosera samples. The DEFB4/103A/104A copy numbers were significantly different between the two sample sets (p = 0.024). Validation of these results, using larger sample sizes as well as samples from other areas of PNG, is warranted. In addition, genetic association studies are needed to estimate the effects of these polymorphisms on HIV infection and disease progression in PNG.

SUBMITTER: Willie B

PROVIDER: S-EPMC6105279 | biostudies-literature | 2017 Mar-Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A preliminary assessment of Toll-like receptor and β-defensin gene polymorphisms in Papua New Guinea - what does it mean for HIV/AIDS?

Willie Barne B Gare Janet J King Christopher L CL Zimmerman Peter A PA Mehlotra Rajeev K RK

Papua and New Guinea medical journal 20170301 1-2

Polymorphisms in Toll-like receptor (TLR) and human β-defensin (hBD, encoded by DEFB) genes have been evaluated for their associations with HIV infection and disease outcomes. Those studies, conducted in various populations under a variety of study designs, generally revealed that specific single nucleotide polymorphisms (SNPs) in TLR1, 2, 3, 4, 6, 7, 8, and 9 genes, and copy number variation (CNV) in DEFB4 (encoding hBD-2), DEFB103A (encoding hBD-3), an ...[more]

PMID: 30147152

Similar Datasets

Project description:BackgroundThe hypothesis is that hemoglobin-based metrics are useful tools for estimating malaria endemicity and for monitoring malaria control strategies. The aim of this study is to compare population hemoglobin mean and anemia prevalence to established indicators of malaria endemicity, including parasite rates, rates of enlarged spleens in children, and records of (presumptive) malaria diagnosis among populations living with different levels of malaria transmission.Methodology/principal findingsConvenience sample, multisite cross-sectional household surveys conducted in Papua New Guinea. Correlations (r(2)) between population Hb mean and anemia prevalence and altitude, parasite rate, and spleen rate were investigated in children ages 2 to 10 years, and in the general population; 21,664 individuals from 156 different communities were surveyed. Altitude ranged from 5 to 2120 meters. In young children, correlations between altitude and parasite rate, population Hb mean, anemia prevalence, and spleen rate were high (r(2): -0.77, 0.73, -0.81, and -0.68; p<0.001). In the general population, correlations between altitude and population Hb mean and anemia prevalence were 0.83 and 0.85, respectively. Among young children, parasite rate correlated highly with anemia prevalence, population Hb mean, and spleen rate (r(2): 0.81, -0.81, and 0.86; p<0.001). Population Hb mean (corrected for direct altitude effects) increased with altitude, from 10.5 g/dl at <500 m to 12.8 g/dl at >1500 m (p<0.001).Conclusions/significanceIn PNG, where Plasmodium vivax accounts for an important part of all malaria infections, population hemoglobin mean and anemia prevalence correlate well with altitude, parasite, and spleen rates. Hb measurement is simple and affordable, and may be a useful new tool, alone or in association with other metrics, for estimating malaria endemicity and monitoring effectiveness of malaria control programs. Further prospective studies in areas with different malaria epidemiology and different factors contributing to the burden of anemia are warranted to investigate the usefulness of Hb metrics in monitoring malaria transmission intensity.

Project description:Polymorphisms in toll-like receptor (TLR) and β-defensin (DEFB) genes have been recognized as potential genetic factors that can influence susceptibility to and severity of periodontal diseases (PD). However, data regarding associations between these polymorphisms and PD are still scarce in North American populations, and are not available in HIV+ North American populations. In this exploratory study, we analyzed samples from HIV+ adults (n = 115), who received primary HIV care at 3 local outpatient HIV clinics and were monitored for PD status. We genotyped a total of 41 single nucleotide polymorphisms (SNPs) in 8 TLR genes and copy number variation (CNV) in DEFB4/103A. We performed regression analyses for levels of 3 periodontopathogens in subgingival dental plaques (Porphyromonas gingivalis [Pg], Treponema denticola [Td], and Tannerella forsythia [Tf]) and 3 clinical measures of PD (periodontal probing depth [PPD], gingival recession [REC], and bleeding on probing [BOP]). In all subjects combined, 2 SNPs in TLR1 were significantly associated with Td, and one SNP in TLR2 was significantly associated with BOP. One of the 2 SNPs in TLR1 was significantly associated with Td in Caucasians. In addition, another SNP in TLR1 and a SNP in TLR6 were also significantly associated with Td and Pg, respectively, in Caucasians. All 3 periodontopathogen levels were significantly associated with PPD and BOP, but none was associated with REC. Instrumental variable analysis showed that 8 SNPs in 6 TLR genes were significantly associated with the 3 periodontopathogen levels. However, associations between the 3 periodontopathogen levels and PPD or BOP were not driven by associations with these identified SNPs. No association was found between DEFB4/103A CNV and any periodontopathogen level or clinical measure in all samples, Caucasians, or African Americans. Our exploratory study suggests a role of TLR polymorphisms, particularly TLR1 and TLR6 polymorphisms, in PD in HIV+ North Americans.

Project description:BACKGROUND:Routine immunization programs face many challenges in settings such as Papua New Guinea with dispersed rural populations, rugged geography and limited resources for transport and health. Low routine coverage contributes to disease outbreaks such as measles and the polio that re-appeared in 2018. We report on an in-depth local assessment that aimed to document immunization service provision so as to review a new national strategy, and consider how routine immunization could be better strengthened. METHODS:In East New Britain Province, over 2016 and 17, we carried out a cross-sectional assessment of 12 rural health facilities, staff and clients. The study was timed to follow implementation of a new national strategy for strengthening routine immunization. We used interview, structured observation, and records review, informed by theory-based evaluation, a World Health Organization quality checklist, and other health services research tools. RESULTS:We documented strengths and weaknesses across six categories of program performance relevant to national immunization strategy and global standards. We found an immunization service with an operational level of staff, equipment and procedures in place; but one that could reach only half to two thirds of its target population. Stronger routine services require improvement in: understanding of population catchments, tracking the unvaccinated, reach and efficiency of outreach visits, staff knowledge of vaccination at birth and beyond the first year of life, handling of multi-dose vials, and engagement of community members. Many local suggestions to enhance national plans, included more reliable on-demand services, integration of other family health services and increased involvement of men. CONCLUSIONS:The national strategy addresses most local gaps, but implementation and resourcing requires greater commitment. Long-term strengthening requires a major increase in centrally-allocated resources, however there are immediate locally feasible steps within current resources that could boost coverage and quality of routine immunization especially through better population-based local planning, and stronger community engagement. Our results also suggest areas where vaccination campaigns in PNG can contribute to routine immunization services.

Dataset Information

A preliminary assessment of Toll-like receptor and ?-defensin gene polymorphisms in Papua New Guinea - what does it mean for HIV/AIDS?

Publications

A preliminary assessment of <i>Toll-like receptor</i> and <i>β-defensin</i> gene polymorphisms in Papua New Guinea - what does it mean for HIV/AIDS?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets