Association of Asthma and Rhinitis with Epigenetics of Coronavirus Related Genes.

INTRODUCTION: Susceptibility factors for coronavirus disease 2019 (COVID-19) include sex and medical conditions such as asthma and rhinitis. DNA methylation (DNAm) is associated with asthma, rhinitis, and several viruses. We examined associations of asthma/rhinitis with DNAm at CpGs located on coronavirus related genes, and if these associations were sex-specific. METHODS: In total, n = 242 subjects aged 26 years from the Isle of Wight Birth Cohort were included in the study. Linear regressions were used to examine sex specific and non-specific associations of DNAm at CpGs on coronavirus related genes with asthma/rhinitis status. Associations of DNAm with gene expression in blood were assessed for functional relevance of identified CpGs. RESULTS: Statistically significant interaction effects of asthma or rhinitis with sex were identified at 40 CpGs for asthma and 27 CpGs for rhinitis. At 21 CpGs, DNAm was associated with asthma, and at 45 CpGs with rhinitis, regardless of sex. Assessment of functional relevance of the identified CpGs indicated a potential of epigenetic regulatory functionality on gene activity at 14 CpGs for asthma and 17 CpGs for rhinitis, and of those 6 CpGs for asthma and 7 CpGs for rhinitis were likely to be sex-specific. CONCLUSION: Subjects with asthma/rhinitis may have altered susceptibility to COVID-19 due to changes in their DNAm associated with these conditions. Sex specificity on association of asthma/rhinitis with DNAm at certain CpGs, and on the association of DNAm at asthma/rhinitis-linked CpGs with gene expression have the potential to explain the reported sex-specificity in COVID-19 morbidity and mortality.

Methylation of Host Genes Associated with Coronavirus Infection from Birth to 26 Years.

DNA methylation (DNAm) patterns over time at 1146 CpGs on coronavirus-related genes were assessed to understand whether the varying differences in susceptibility, symptoms, and the outcomes of the SARS-CoV-2 infection in children and young adults could be explained through epigenetic alterations in a host cell's transcriptional apparatus to coronaviruses. DNAm data from the Isle of Wight birth cohort (IOWBC) at birth, 10, 18, and 26 years of age were included. Linear mixed models with repeated measurements stratified by sex were used to examine temporal patterns, and cluster analysis was performed to identify CpGs following similar patterns. CpGs on autosomes and sex chromosomes were analyzed separately. The association of identified CpGs and expression of their genes were evaluated. Pathway enrichment analyses of the genes was conducted at FDR = 0.05. DNAm at 635 of the 1146 CpGs on autosomes showed statistically significant time effects (FDR = 0.05). The 635 CpGs were classified into five clusters with each representing a unique temporal pattern of DNAm. Of the 29 CpGs on sex chromosomes, DNAm at seven CpGs in males and eight CpGs in females showed time effects (FDR = 0.05). Sex-specific and non-specific associations of DNAm with gene expression were found at 24 and 93 CpGs, respectively. Genes which mapped the 643 CpGs represent 460 biological processes. We suggest that the observed variability in DNAm with advancing age may partially explain differing susceptibility, disease severity, and mortality of coronavirus infections among different age groups.

Variations in Serum Free Thyroxine Concentration Within the Reference Range Predicts the Incidence of Metabolic Syndrome in Non-Obese Adults: A Cohort Study.

BACKGROUND: The association of changes in thyroid hormone values over time with the incidence of metabolic syndrome (MetS) has not yet been evaluated. For the first time, this study assessed the effect of thyroid hormone variations in the subclinical and euthyroid range on the incidence of MetS and its components over a 10-year follow-up in an adult population. METHODS: Data were analyzed from the prospective population-based Tehran Thyroid Study. Of 5786 randomly selected subjects aged ≥20 years, after excluding subjects with MetS (n = 1403), those with serum thyrotropin (TSH) >10 or <0.1 mIU/L (n = 104), those taking thyroid drugs (n = 85) or corticosteroids (n = 97), those with a body mass index (BMI) <18.5 kg/m2, those with a glomerular filtration rate <30, and those with a history of cancer (12), data for 2393 subjects were analyzed. Body weight, waist circumference, and blood pressure were measured, and serum concentrations of lipids and lipoproteins, fasting blood glucose, insulin, free thyroxine (fT4), and TSH were assayed at baseline and during three follow-up studies at three-year intervals. MetS was determined using definition of the Joint Interim Statement, adjusted for the Iranian population. RESULTS: An increase in fT4 values overtime was associated with lower odds of abdominal obesity (odds ratio [OR] = 0.49 [confidence interval (CI) 0.35-0.69]) and hypertriglyceridemia (OR = 0.57 [CI 0.41-0.78]), and with higher odds of hypertension (OR = 1.35 [CI 1.05-1.74]), adjusted for age, sex, smoking, BMI, and Homeostasis Model Assessment Index for Insulin Resistance. fT4 was associated with lower odds of MetS in the crude model, and after adjustment for age, sex, and smoking (OR = 0.59 [CI 0.39-0.9]). This association lost its significance after further adjusting for BMI. In a subgroup analysis of obese (i.e. BMI ≥30 kg/m2) and non-obese (i.e., BMI <30 kg/m2) subjects, fT4 was a significant predictor of MetS only in non-obese subjects after adjusting for age, sex, and smoking (ß = 0.49 [CI 0.29-0.83], p = 0.007) and also after further adjustment for Homeostasis Model Assessment Index for Insulin Resistance (ß = 0.57 [CI 0.34-0.96], p = 0.03). Serum TSH variations over time were not associated with any of the MetS components or with odds of MetS. CONCLUSION: A decrease in serum fT4 values is associated with an increased risk for MetS, especially in non-obese adults.

Missing Elements in Surgical Pathology Reports: Breast, Colon and Stomach Cancers.

Cancer pathology reports play an important role in choice of patient care. They provide crucial information concerning diagnosis, therapy options, and prognosis. Professional pathology institutions, such as the College of American Pathologists (CAP), have developed checklists to ensure the presence of all the required elements in reports. In this study, 438 surgical pathology reports of patients with breast (148), colon (147), and stomach cancer (143) were evaluated with respect to the presence of mandated elements according to CAP checklists. The most common missing element in all the three types of cancer was 'staging' (73.6, 53.1, and 56.6% in breast, colon, and stomach cancer reports missed 'staging', respectively). The second most missing element was 'tumor site' in breast (64.2%) and stomach cancer (30.1%), and 'procedure' in colon cancer (29.3%). 'Perineural invasion' was the third most missing element in the three types of cancer (25.7, 17.0, and 22.4% in breast, colon, and stomach cancer, respectively). Only 11.4% of reports included all key elements required by CAP. The use of checklists was associated with higher rate of completeness. This study demonstrates that the key elements requiring the information on the requisition forms from the clinicians are commonly missed, leading to ambiguity.