Immunogenicity and safety of quadrivalent influenza vaccine among young and older adults in Tianjin, China: implication of immunosenescence as a risk factor.

BACKGROUND: Older adults are more vulnerable to seasonal influenza than younger adults. The immune responses of older persons to the influenza vaccine are usually poorer than those of young individuals, which is hypothesized due to immunosenescence. We conducted a study to evaluate the immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4) in a total of 167 young (< 65 years, n = 79) and older (≥ 65 years, n = 88) adults from October 2021 to March 2022 in Tianjin, China. A single dose was administered to all participants. Blood samples were collected and strain-specific hemagglutination inhibition (HAI) antibody titers were measured before and 21 to 28 days after vaccination. Safety information was also collected for 28 days and 6 months after vaccination. Differences in immunogenicity and safety were compared between young and old age groups, and multivariate logistic regression was used to estimate the effect of age and other factors on HAI antibody responses. RESULTS: Overall, geometric mean titers (GMTs) against all four vaccine strains in older adults were lower than those in the young, whereas the seroconversion rates (SCRs) were similar. Multivariate logistic regression analysis showed that age, influenza vaccination history, and pre-vaccination HAI titers were independent factors affecting SCRs and seroprotection rates (SCRs). Older age had significant negative impact on SCRs against H1N1 (OR, 0.971; 95% CI: 0.944-0.999; P = 0.042) and B/Victoria (OR, 0.964; 95% CI: 0.937-0.992; P = 0.011). In addition, there was a significant negative correlation between chronological age (years) and post-vaccination HAI titers against H1N1 (rho = -0.2298, P < 0.0001), B/Victoria (rho = -0.2235, P = 0.0037), and B/Yamagata (rho = -0.3689, P < 0.0001). All adverse events were mild (grade 1 or grade 2) that occurred within 28 days after vaccination, and no serious adverse event was observed. CONCLUSIONS: IIV4 is immunogenic and well-tolerated in young and older adults living in Tianjin, China. Our findings also indicate that age is an independent factor associated with poorer humoral immune responses to IIV4.

Genetic polymorphisms in lncRNAs predict recurrence of ischemic stroke.

Genetic polymorphisms in long non-coding RNAs (lncRNAs) are considered as potential genetic biomarkers for the prediction of human complex diseases such as ischemic stroke (IS). However, so far, no reports have focused on the relationship of lncRNA polymorphisms with IS onset and prognosis. In our study, eight potential functional polymorphisms of four well-known lncRNAs (H19 rs2107425 and rs2251375, MALAT1 rs4102217 and rs3200401, MEG3 rs11160608 and rs4081134, SENCR rs4526784 and rs555172) were genotyped in 657 ischemic stroke patients. Then, the association between lncRNA polymorphisms and IS onset and recurrence were investigated. These lncRNA variants were not associated with age onset of IS. However, we observed that MEG3 rs4081134 AA genotype was statistically related with a reduced risk of stroke recurrence, particularly for patients with large-artery atherosclerotic stroke. Also, the decreased risk was more prominent in elders, non-smokers, non-drinkers and hypertensive patients. Furthermore, the variant genotype AA of rs4081134 was an independent predictor for IS recurrence using the multivariate Cox regression model. Our findings indicated that MEG3 rs4081134 can serve as a useful biomarker and potential therapeutic target in IS recurrence. More researches are needed to verify our results and explore the underlying molecular mechanisms.

Genetic variants in migraine: a field synopsis and systematic re-analysis of meta-analyses.

OBJECTIVE: Numerous genetic variants from meta-analyses of observational studies and GWAS were reported to be associated with migraine susceptibility. However, due to the random errors in meta-analyses, the noteworthiness of the results showing statistically significant remains doubtful. Thus, we performed this field synopsis and re-analysis study to evaluate the noteworthiness using a Bayesian approach in hope of finding true associations. METHODS: Relevant meta-analyses from observational studies and GWAS examining correlation between all genetic variants and migraine risk were included in our study by a PubMed search. Identification of noteworthy associations were analyzed by false-positive rate probability (FPRP) and Bayesian false discovery probability (BFDP). Using noteworthy variants, GO enrichment analysis were conducted through DAVID online tool. Then, the PPI network and hub genes were performed using STRING database and CytoHubba software. RESULTS: As for 8 significant genetic variants from observational studies, none of which showed noteworthy at prior probability of 0.001. Out of 47 significant genetic variants in GWAS, 36 were noteworthy at prior probability of 0.000001 via FPRP or BFDP. We further found the pathways "positive regulation of cytosolic calcium ion concentration" and "inositol phosphate-mediated signaling" and hub genes including MEF2D, TSPAN2, PHACTR1, TRPM8 and PRDM16 related to migraine susceptibility. CONCLUSION: Herein, we have identified several noteworthy variants for migraine susceptibility in this field synopsis. We hope these data would help identify novel genetic biomarkers and potential therapeutic target for migraine.

Association between microRNA binding site polymorphisms in immunoinflammatory genes and recurrence risk of ischemic stroke.

MicroRNA binding site polymorphisms in immunoinflammatory genes have been implicated as candidate biomarkers for prediction of complex human diseases. However, the roles of microRNA binding site polymorphisms in stroke onset and prognosis remain unclear. Thus, for the first time, five potential functional polymorphisms in immunoinflammatory genes (CXCR2 rs1126579, TLR4 rs11536889, ADIPOR2 rs12342, MMP-2 rs7201 and MMP-9 rs1056628) were genotyped in 657 patients with ischemic stroke. These five polymorphisms were not related with age onset of ischemic stroke. However, we found that ADIPOR2 rs12342 was significantly associated with a decreased recurrence risk, especially for the patients with small-vessel disease. Moreover, by using multivariate Cox regression, the variant genotype GG/GA of rs12342 was observed as an independent protective factor for stroke recurrence, even after Bonferroni correction. In addition, after the addition of rs12342 in the model with clinical factors, the new model showed the improved discriminatory ability to predict stroke recurrence. In short, our results suggested that ADIPOR2 rs12342 may be a novel genetic biomarker and therapeutic target for ischemic stroke recurrence. Further studies are required to replicate our findings and clarify the potential biological mechanism.

Association between 12p13 Polymorphisms and Ischemic Stroke in Asian Populations: New Evidence from a Case-Control Study and a Meta-Analysis.

A genome-wide association study first reported the association between ischemic stroke risk and two polymorphisms on chromosome 12p13: rs12425791 and rs11833579. Since then, a series of studies have investigated the association of these two polymorphisms with stroke risk, but the results were inconsistent even in Asian populations. Thus, we carried out a case-control study to uncover the potential relationship, and then conducted a meta-analysis to further address the issue. 540 ischemic stroke patients and 540 unrelated controls were enrolled in the case-control study. Genotyping was accomplished by polymerase chain reaction-ligation detection reaction. The meta-analysis was conducted by combining our study with previous published data. In our case-control study, the significant association was observed between ischemic stroke and rs12425791 (AG vs. GG: OR = 1.32, P < 0.05) but not rs11833579. When pooled with previous studies, the significant relationship of rs12425791 with ischemic stroke was found (A vs. G: OR = 1.07, P < 0.05; AA + AG vs. GG: OR = 1.10, P < 0.05) in Asian populations, as well as in subgroup analysis. A correlation approaching significance was identified between ischemic stroke risk and rs11833579 (AA + AG vs. GG: OR = 1.06, P = 0.05). New evidence from this case-control study and meta-analysis indicates that 12p13 rs12425791/rs11833579 polymorphisms are associated with ischemic stroke susceptibility in Asian populations.

An updated analysis with 45,078 subjects confirms the association between SNCA rs11931074 and Parkinson's disease.

Large-scale genome-wide association study (GWAS) has identified that the alpha-synuclein (SNCA) rs11931074 polymorphism is associated with Parkinson's disease (PD) susceptibility in individuals of Japanese descent. Subsequently, a number of replication studies have been performed in Asian and Caucasian populations. However, the results remain controversial due to the relatively small sample sizes and genetic heterogeneity. Here, to overcome the limitations of individual studies, we reevaluated this association with data from 33 independent studies involving 15,368 patients and 29,710 control samples identified by searching PubMed and EMBase databases. Odds ratios (OR) with 95% confidence interval (CI) were applied to assess the association between SNCA rs11931074 polymorphism and PD. Heterogeneity, sensitivity analysis, and publication bias were conducted to measure the robustness of our findings. Using allele, recessive, dominant, and additive models, we did not reveal significant heterogeneity among 33 studies. Significant association of the SNCA rs11931074 polymorphism with PD was observed (T vs. G: OR = 1.36, 95% CI = 1.31-1.42; TT vs. TG + GG: OR = 1.58, 95% CI = 1.46-1.72; TT + TG vs. GG: OR = 1.44, 95% CI = 1.35-1.55; TT vs. GG: OR = 1.87, 95% CI = 1.68-2.09) in the pooled populations. Furthermore, subgroup analyses accounting for ethnicity found similar significant results in both Asian and Caucasian populations. In conclusion, our meta-analysis further indicates that the SNCA rs11931074 polymorphism contributes to PD susceptibility. We believe that our findings will be very useful for future genetic studies on PD.