Public Health Genomics最新文献

Background: Sirtuin 6 gene (SIRT6) is a longevity gene that is involved in a variety of metabolic pathways, but the relationship between SIRT6 methylation and longevity has not been clarified.

Methods: We conducted a case-control study on 129 residents with a family history of longevity (1 of parents, themselves, or siblings aged ≥90 years) and 86 individuals without a family history of exceptional longevity to identify the association. DNA pyrosequencing was performed to analyze the methylation status of SIRT6 promoter CpG sites. qRT-PCR and ELISA were used to estimate the SIRT6 messenger RNA (mRNA) levels and protein content. Six CpG sites (P1-P6) were identified as methylation variable positions in the SIRT6 promoter region.

Results: At the P2 and P5 CpG sites, the methylation rates of the longevity group were lower than those of the control group (p < 0.001 and p = 0.009), which might be independent determinants of longevity. The mRNA and protein levels of SIRT6 decreased in the control group (p < 0.0001 and p = 0.038). The mRNA level negatively correlated with the methylation rates at the P2 (rs = -0.173, p = 0.011) and P5 sites (rs = -0.207, p = 0.002). Furthermore, the protein content positively correlated with the methylation rate at the P5 site (rs = 0.136, p = 0.046) but showed no significant correlation with the methylation rate at the P2 site.

Conclusion: The low level of SIRT6 methylation may be a potential protective factor of Chinese longevity.

Background: Human genetic resources are an important material component for life science research and have strategic significance for medical science and technological innovation. In this study, we employ frameworks from social psychology and the science of human behavior to study human genetic resource providers.

Aims: We used structural equation techniques to explain factors affecting the intention to provide human genetic resources and the mechanisms for providing such resources.

Methods: We conducted an online survey with respondents from ethnic minorities (n = 912). Our model integrates key variables informed by the theory of planned behavior (TPB), the theory of benefit and risk assessment (BRA), as well as variables that represent the policy and political system.

Results: Our results show that the factors affecting the intention to provide human genetic resources, ranked from highly influential to less influential, are perceived benefits, privacy risk, attitudes toward providing human genetic resources, perceived behavioral efficacy, psychological risk, subjective norms, and physical risk. The variables informed by the TPB all have a significant positive effect on the intention to provide human genetic resources. With the exception of physical risk, the variables informed by the theory of BRA have a significant effect on the intention to provide human genetic resources. Respondents with different health conditions have significantly different levels of physical risk.

Conclusions: The results of our study provide insights into how to improve people's intention to provide human genetic resources. We also proposed ways to protect such resources globally.

Background: Diabetes is one of the most common metabolic diseases in humans that cause disruption in glucose and fat metabolism. The determination of the ABO blood group system is hereditary and both diabetes and blood groups have a genetic basis.

Objectives: The aim of this study was to investigate the odds of type 2 diabetes for some blood groups.

Methods: This case-control study was conducted in hospitals of Kermanshah in 2018. The case group consisted of patients with diabetes admitted to hospital and the control group of nondiabetic patients hospitalized in the surgical ward. Information such as age, sex, BMI, family history of diabetes and blood group is collected and analyzed by the univariate and multivariate logistic regression method.

Results: A total of 750 patients were enrolled in this study. The number of participants in both groups was 375. The average ages of the participants were 50.51 and 51.62 years, respectively. 67.5% of the patients in the case group were female in comparison with 73.6% of those in the control group. The value of Rh+ in the case and control groups was 94.4 and 93.6%, respectively (p = 0.645). The chance of having diabetes for patients with blood group A was 76% higher than for those with blood group O (p = 0.006).

Conclusion: According to the results of this study, the odds of type 2 diabetes for people in blood group A was higher than for those in other blood groups. It is recommended that blood group A be considered as a risk factor in the screening of type 2 diabetes.

Aims: This study was undertaken to examine how a layperson is likely to interpret genetic information delivered in a clinical setting.

Methods: A novel survey was designed to engage the reader in a simulated discussion of heritability as it might relate to human disease. The survey took approximately 5 min to administer. 307 individuals of different backgrounds completed the survey in the outpatient waiting room on their cell phone.

Results: Overall, basic knowledge of inheritance and the concepts of heredity scored very well in the study cohort. Both knowledge and interpretation questions were answered correctly more often than not. There was generally no association between the scores on survey and gender or age.

Conclusions: People recognize the basic concepts of heritability but struggle with real-life interpretations and more nuanced concepts of heredity.

Introduction: Genomic tests can predict risk and tailor screening recommendations for colorectal cancer (CRC). Primary care could be suitable for their widespread implementation.

Objective: We aimed to assess the feasibility and acceptability of administering a CRC genomic test in primary care.

Methods: Participants aged 45-74 years recruited from 4 Australian general practices were offered a genomic CRC risk test. Participants received brief verbal information about the test comprising 45 CRC-associated single-nucleotide polymorphisms, before choosing whether to undertake the test. Personalized risks were given to testers. Uptake and knowledge of the genomic test, cancer-specific anxiety (Cancer Worry Scale), psychosocial impact (Multidimensional Impact of Cancer Risk Assessment [MICRA] score), and impact on CRC screening behaviour within 6 months were measured.

Results: In 150 participants, test uptake was high (126, 84%), with 125 (83%) having good knowledge of the genomic test. Moderate risk participants were impacted more by the test (MICRA mean: 15.9) than average risk participants (mean: 9.5, difference in means: 6.4, 95% confidence interval (CI): 1.5, 11.2, p = 0.01), but all scores were low. Average risk participants' cancer-specific anxiety decreased (mean differences from baseline: 1 month -0.5, 95% CI: -1.0, -0.1, p = 0.03; 6 months -0.6, 95% CI: -1.0, -0.2, p = 0.01). We found limited evidence for genomic testers being more likely to complete the risk-appropriate CRC screening than non-testers (41 vs. 17%, odds ratio = 3.4, 95% CI: 0.6, 34.8, p = 0.19), but some mediators of screening behaviour were altered in genomic testers.

Conclusions: Genomic testing for CRC risk in primary care is acceptable and likely feasible. Further development of the risk assessment intervention could strengthen the impact on screening behaviour.

Introduction: The presence of Merkel cell polyomavirus (MCPyV) was identified in Merkel cell carcinoma (MCC). However, there was sparse information on the link of other common nonmelanoma skin cancers - basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) - to MCPyV infection. The current study describes the phylogenetic information of MCPyV isolated from Iranian non-MCC (nonmelanoma skin cancers) focusing on tumorigenesis of mutations in large tumor (LT) antigen (LT-Ag) fragment.

Methods: Sixty patients with BCC and 20 patients with SCC were included in this study (48 males and 32 females; average age 65 years). The MCPyV-DNA copy number in positive samples was measured by quantitative real-time PCR. Then, mutational analysis of the MCPyV LT gene was carried out by direct sequencing.

Results: While MCPyV DNA was detected in 6 (10%) of 60 BCC samples, no viral genome was found in SCCs. There was no distinct association of MCPyV positivity with gender, age, or type of tumor (BCC or SCC) (p value >0.05). Quantitative real-time PCR revealed that the median number of viral DNA copies per cell was 0.7 in 6 MCPyV-positive BCC samples. Furthermore, full-length LT-Ag sequencing of positive samples indicated no stop codon or frameshift mutations compared to reference sequences.

Conclusion: Considering the important role of the LT-Ag in the pathogenicity of MCPyV, non-synonymous mutations compared with the reference proteins triggered relevant amino acid substitutions. Overall, the results showed no tumor-associated mutations in the LT-Ag sequence of MCPyVs from positive samples.

Introduction: Genetic risk modifier testing (GRMT), an emerging form of genetic testing based on common single nucleotide polymorphisms and polygenic risk scores, has the potential to refine estimates of BRCA1/2 mutation carriers' breast cancer risks. However, for women to benefit from GRMT, effective approaches for communicating this novel risk information are needed.

Objective: To evaluate patient preferences regarding risk communication materials for GRMT.

Methods: We developed four separate presentations (panel of genes, icon array, verbal risk estimate, graphical risk estimate) of hypothetical GRMT results, each using varying risk communication strategies to convey different information elements including number of risk modifier variants present, variant prevalence among BRCA1/2 carriers, and implications and uncertainties of test results for cancer risk. Thirty BRCA1/2 carriers evaluated these materials (randomized to low, moderate, or high breast cancer risk versions). Qualitative and quantitative data were obtained through in-person interviews.

Results: Across risk versions, participants preferred the presentation of the graphical risk estimate, often in combination with the verbal risk estimate. Interest in GRMT was high; 76.7% of participants wanted their own GRMT. Participants valued the potential for GRMT to clarify their cancer susceptibility and provide actionable information. Many (65.5%) anticipated that GRMT would make risk management decisions easier.

Conclusions: Women with BRCA1/2 mutations could be highly receptive to GRMT, and the minimal amount of necessary information to be included in result risk communication materials includes graphical and verbal estimates of future cancer risk. Findings will inform clinical translation of GRMT in a manner consistent with patients' preferences.

Introduction: Genetic variations in the slow component of the delayed rectifier potassium channels (IKs) are reported to contribute to an increased susceptibility to arrhythmias. This study aims to investigate the frequency and the possible association of the rs2236609 polymorphism in the KCNE1 gene and the risk of atrial fibrillation (AF).

Methods: This was a case-control study that recruited 100 patients suffering from AF (mean age 49.4 ± 15.1 years), and a control group of 95 healthy participants older than 55 years (mean age 59.8 ± 4.1 years) with no history of cardiovascular disease, hypertension, or diabetes. Genomic DNA was extracted from whole peripheral blood, and the desired fragment was amplified using polymerase chain reaction followed by restriction digestion with the NspI restriction enzyme.

Results: The results showed a significant difference between the single-nucle-otide polymorphism variations in AF patients and controls (p < 0.022). The risk of AF in the GG genotype was significantly decreased (odds ratio [OR] 0.42; 95% confidence interval [Cl] 0.23-0.79). The risk of AF in the GA (OR 2.12; 95% Cl 1.11-4.06) and AA (OR 2.28, 95% Cl 0.57-9.1) genotypes was significantly increased. The odds of developing AF according to A allele counting was significantly increased (OR 2.1; 95% Cl 1.2608-3.638; p = 0.0048).

Conclusion: Our results showed a significant increase in AF risk in people carrying the A allele, while the G allele might be considered as a protective allele.