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The Laryngoscope Jul 2020P2RX2 encoding P2X purinoreceptor 2 has been identified as the gene responsible for autosomal dominant deafness-41 (DFNA41) as well as mediating vulnerability to...
OBJECTIVES/HYPOTHESIS
P2RX2 encoding P2X purinoreceptor 2 has been identified as the gene responsible for autosomal dominant deafness-41 (DFNA41) as well as mediating vulnerability to noise-induced hearing loss (NIHL). The objective of this study was to investigate the audiological and molecular characteristics of P2RX2-related deafness, with emphasis on its role in NIHL by determining the audiological characteristics of a previously reported six-generation DFNA41 family with a 10-year follow-up. We have also summarized phenotype-genotype correlations of P2RX2-related deafness in human and mouse models.
STUDY DESIGN
We describe clinical longitudinal follow-up in the DFNA41 family with P2RX2 (p.Val60Leu) mutation and perform a systematic literature search in PubMed and poster presentations on meeting/conference websites to identify current insights into P2RX2-mediated NIHL.
METHODS
Clinical and physical examinations of the family members were performed, and audiograms were obtained to assess the hearing thresholds. Clinical follow-up features in this DFNA41 family are presented along with correlation analyses of phenotype-genotype in all reported families with P2RX2-related deafness.
RESULTS
Progressive hearing impairment was confirmed by history and by audiological follow-up testing in all the patients. The onset of hearing loss was between age 25 and 35 years. All affected subjects had bilateral sensorineural hearing loss involving all frequencies with some significant gender differences.
CONCLUSIONS
Our study and the review of the literature suggest that P2RX2 plays a crucial role in predisposition to noise-induced and age-related hearing loss. A better knowledge about the P2RX2-associated genetic variants can help in developing novel therapeutic strategies.
LEVEL OF EVIDENCE
2b Laryngoscope, 130:1657-1663, 2020.
Topics: Adult; Disease Progression; Female; Follow-Up Studies; Genotype; Hearing Loss, Sensorineural; Humans; Longitudinal Studies; Male; Middle Aged; Mutation; Pedigree; Phenotype; Receptors, Purinergic P2X2; Sex Factors
PubMed: 31593348
DOI: 10.1002/lary.28318 -
Platelets 2020Cigarette smoking is an important cardiovascular risk factor, causing morbidity and mortality. There are many original studies on the impact of smoking, but its... (Meta-Analysis)
Meta-Analysis
Cigarette smoking is an important cardiovascular risk factor, causing morbidity and mortality. There are many original studies on the impact of smoking, but its influence on platelet ADP-P2Y12 receptor inhibitors lack consistency. Thus, we conducted a systematic review and meta-analysis of already existing data/studies to further explore this issue. PubMed, Web of science, EMBASE, Clinical Trials, and the Cochrane Library were searched from inception to March 2018. Studies investigating the residual platelet reactivity categorized by smoking status and patients treated with platelet ADP-P2Y12 receptor inhibitors qualified the inclusion criteria. The primary outcome was P2Y12 reaction unit (PRU) value measured by VerifyNow P2Y12 assay, compared with different smoking status in ADP-P2Y12 receptor inhibitors treatment groups. Secondary outcome was post-treatment with 5 μmol/L ADP-inhibition of platelet aggregation (ADP-IPA) measured by light transmittance aggregometry (LTA). Of the 4954 citations retrieved, 12 studies involving 16 296 patients with acute coronary syndrome and/or stent deployment using platelet ADP-P2Y12 receptor inhibitors were included for meta-analysis. Pooled analysis revealed that PRU values of current smokers were 25.70 lower than nonsmokers (95% CI -38.81 to -12.60, = 0.0001), getting better effects of antiplatelet treatment. In the smoking extent subgroup analysis, patients smoking >10 cigarettes/day shown about 46.49 lower of PRU values than patients smoking <10 cigarettes/day ( < 0.00001). Racial subgroup analyses found that smokers had increased platelet inhibition in the Caucasian population. Further, pooled analysis of ADP-IPA values for 1658 patients from five studies showed a significantly lower residual platelet reactivity in current smokers compared to that in nonsmokers (MD = -4.19; 95% CI -6.55 to -1.83; = 0.0005). This systematic review and meta-analysis suggested that smokers have increased platelet inhibition and lower aggregation in response to clopidogrel than nonsmokers. These residual platelet reactivity observations may help to explain differential clinical outcomes in smokers vs. nonsmokers in large scale clinical trials.
Topics: Adult; Aged; Biomarkers; Blood Platelets; Clopidogrel; Humans; Middle Aged; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Publication Bias; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Smoking
PubMed: 30744477
DOI: 10.1080/09537104.2019.1572878