Short stature-related single-nucleotide polymorphism (SNP) activates endothelial repair activity in elderly Japanese

Background: Hypertension and atherosclerosis are bidirectionally related, while platelet count could serve as an indicator of endothelial repair. Therefore, high platelet counts could be associated with hypertension by indicating more intense endothelial repair activity. Furthermore, short stature has been shown to constitute a risk of atherosclerosis. Since inflammation-related single-nucleotide polymorphism (SNP(rs3782886)) is reportedly associated with myocardial infarction and short stature, rs3782886 could be associated with a high platelet count and thus more intense endothelial repair activity. Methods: We conducted a cross-sectional study of 988 elderly Japanese who participated in a general health check-up. Short stature was defined as a height of at or under the 25th percentile of the study population, and high platelet count as the highest tertiles of the platelet levels. Results: High platelet counts were found to be independently and positively associated with hypertension while rs3782886 was independently associated with high platelet levels and short stature. The classical cardiovascular risk factor-adjusted odds ratio (OR) and 95% confidence interval (CI) of high platelet count for hypertension was 1.34 (1.02, 1.77). With non-minor homo of the rs3782886 as the reference group, the adjusted OR and 95% CI for high platelet count and short stature of minor home were 2.40 (1.30, 4.42) and 2.21 (1.16, 4.21), respectively. Conclusion: SNP (rs3782886) was shown to be associated with high platelet count and short stature. This result partly explains how a genetic factor can influence the impact of height on endothelial repair

Association between Epstein-Barr virus serological reactivation and psychological distress: a cross-sectional study of Japanese community-dwelling older adults

Reactivation of Epstein-Barr virus (EBV) is associated with the etiopathogenesis of a broad spectrum of diseases. This study aimed to investigate the association between psychological distress and EBV serological reactivation among community-dwelling older people and assess the role of sex differences in this association. This population-based cross-sectional survey was conducted among individuals who underwent annual health checkups (N = 2,821; median age 72.4 years). EBV serological reactivation was defined as elevation of EBV early antigen immunoglobulin G titers, and psychological distress was defined as Kessler 6 scores ≥5. Multivariable logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (CI) for EBV serological reactivation and psychological distress. EBV serological reactivation and psychological distress were detected in 16.4% and 8.7% of participants, respectively. Women accounted for 71% (328/463) of those with EBV serological reactivation. Multivariable logistic regression analysis showed psychological distress was not significantly associated with EBV serological reactivation among all participants (OR 1.31, 95% CI: 0.95, 1.82; P = 0.102). A sex-stratified multivariable analysis showed a positive association among women (OR 1.45, 95% CI: 1.01, 2.08; P = 0.043), but no association among men. EBV serological reactivation was independently associated with psychological distress in community-dwelling older women. The sex difference in our results warrants further investigation to clarify the physiological mechanisms underlying the association

Successful treatment of chronic lupus myocarditis with prednisolone and mizoribine

A 36-year-old female patient who was diagnosed with chronic myocarditis as an initial manifestation of systemic lupus erythematosus (SLE) was admitted to our hospital. At her third occurrence of heart failure, we performed an endomyocardial biopsy and proved chronic myocarditis with SLE. Subsequently, she was treated with prednisolone and the immunosuppressive agent mizoribine (MZR), and her cardiac function improved. We describe for the first time treatment with MZR for chronic cardiac involvement of SLE

Distinguishing the cerebrospinal fluid cytokine profile in neuropsychiatric systemic lupus erythematosus from other autoimmune neurological diseases

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication in SLE. Although the mechanism of NPSLE remains unclear, cytokines and chemokines are considered to be involved in their pathogenesis. Here we used Bio-Plex Pro assays to examine 27 types of cytokines and chemokines in the cerebrospinal fluid (CSF) of 32 NPSLE patients. We used the CSF of 20 patients with multiple sclerosis (MS) and 22 patients with neuromyelitis optica (NMO) as a disease control group. Fourteen of 27 cytokines/chemokines were significantly higher in the NPSLE patients compared to the MS/NMO patients. We could identify six "minimum predictive markers" by using a weighted-voting algorithm that could distinguish NPSLE from MS and NMO: interleukin (IL)-17, IL-2, interferon (IFN)-γ, IL-5, basic fibroblast growth factor (FGF)-basic and IL-15. The determination of various types of CSF cytokine profiles may contribute to the diagnosis of NPSLE and may help elucidate the mechanisms underlying this disease

Identification of risk factors for elevated serum IgG4 levels in subjects in a large-scale health checkup cohort study

Introduction: To allow the identification of IgG4-related disease (IgG4-RD) from a subclinical phase as it is important to understand the risk of elevated serum IgG4 levels. We planned to evaluate serum IgG4 levels in the participants of the Nagasaki Islands Study (NaIS), a large-scale health checkup cohort study.Methods: This study included 3,240 individuals who participated in the NaIS between 2016 and 2018 and consented to participate in the study. Serum IgG4, IgG, and IgE levels and human leukocyte antigen (HLA) genotyping results of the NaIS subjects as well as lifestyle habits and peripheral blood test results were analyzed. The magnetic bead panel assay (MBA) and the standard nephelometry immunoassay (NIA) were used to measure serum IgG4 levels. The data were evaluated using multivariate analysis to identify lifestyle and genetic factors associated with elevated serum IgG4 levels.Results: Serum IgG4 levels measured with the NIA and MBA showed a tight positive correlation between the two groups (correlation coefficient 0.942). The median age of the participants in the NaIS was 69 years [63–77]. The median serum IgG4 level was 30.2 mg/dL [IQR 12.5–59.8]. Overall, 1019 (32.1%) patients had a history of smoking. When the subjects were stratified into three groups based on the smoking intensity (pack-year), the serum IgG4 level was significantly higher among those with a higher smoking intensity. Accordingly, the multivariate analysis identified a significant relationship between smoking status and serum IgG4 elevation.Conclusion: In this study, smoking was identified as a lifestyle factor correlating positively with elevated serum IgG4 levels

Association between mental health and bone mass among community-dwelling adults: Nagasaki Islands Study on bone health

Osteoporosis and its related fractures are important public health issues. This study examined the association between the Kessler Psychological Distress Scale (K6) and low bone mass in middle-aged community-dwelling men and women. A crosssectional study was nested in a prospective observational study of 1,101 participants (median age: 57 [49-62] years in men and 58 [50-62] years in women) residing in a rural city in western Japan. Participants were recruited during medical check-ups in 2016 and 2017 from the community-dwelling population. The bone mass of the calcaneus was evaluated using quantitative ultrasound. Of the participants, 56 men (14.9%) and 144 women (19.9%) had a bone mass of less than 70% of the mean of young adults. Univariate analysis revealed that there was a trend toward lower body mass index (BMI) and higher prevalence of low bone mass with an increase in K6 scores in men but not in women. Logistic regression analysis, adjusting for possible confounders(age, BMI, smoking, drinking habits, exercise habits, diabetes, hyperlipidemia, and hypertension), showed significant associations between the K6 scores and low bone mass (odds ratio (OR) = 2.66 for the men with 5 to 12 points of K6, OR = 7.51 for men with ≥ 13 of K6, not for women). We showed an association between psychological distress and low bone mass independent of cofounders among community-dwelling middle-aged men but not women. This suggests that healthy mental health in middle-aged men may be a possible target for the prevention of consequent osteoporosis or fragile bone fractures

Association of FTO genotype with obesity and bone health among communitydwelling adults ; Goto Island study on bone health

Bone mass is tuned by various factors, including aging, menopause, low body weight, and genetic variations. Here, we showed an independent association between a genotype on the fat mass- and obesity-associated FTO gene (#610966 on OMIM) and bone loss after adjusting for age and body mass index (BMI). A cross-sectional study was nested in a prospective observational study of 1,828 participants (median age: 69 [62-76] years in men and 68 [61-75] years in women) residing in a rural city in western Japan (Goto Island study). Participants were recruited during medical checkups in 2014 and 2016 from the community-dwelling population. The bone mass of the calcaneus was evaluated using quantitative ultrasound. The single nucleotide polymorphism (SNP) rs1421085 was genotyped using a hydrolysis probe. The chi-squared test was used to determine whether the variants were in equilibrium in this population. There were differences in medians of BMI among the genotypes (24.3 in CC, 23.0 in CT, and 22.6 in TT, P = 0.01), but not in those of bone mass. There was a significant association between the minor allele (C) and being overweight in a gene dosage-dependent manner (BMI > 25, OR per allele =1.52, 95% CI = 1.07-2.14, P = 0.02 in men, OR = 1.48, 95% CI = 1.16-1.95, P = 0.01 in women). Logistic regression analysis showed a significant protective association in male carriers of the minor allele against low bone mass (QUS T-score less than -2.0) after adjusting for age and BMI in men aged 65-75 years (OR = 0.50, 95% CI = 0.27-0.96, P = 0.036), with no significant association in women.Our study indicated an association between the genetic polymorphism of FTO and bone mass among community-dwelling men aged 65-75 years. The polymorphism may play a role in bone health with higher BMI and other beneficial functions

Association between self-reported walking speed and calcaneal stiffness index in postmenopausal Japanese women

Background: Osteoporosis and related fractures, a worldwide public health issue of growing concern, is characterized by compromised bone strength and an increased risk of fracture. Here we show an association between self-reported walking speed and bone mass among community-dwelling postmenopausal Japanese women aged 50 years and older. Design; cross-sectional study: Setting and Participants; The survey population included 1008 postmenopausal women 50?92 years of age residing in rural communities. Methods: Self-reported walking speed was ascertained by asking the participants: “Is your walking speed faster than others of the same age and sex?” to which participants responded “yes (faster)” or “no (moderate/slower).” Calcaneal stiffness index was measured. Results: Women with a faster self-reported walking speed were younger and had a lower BMI, higher stiffness index, and higher grip strength than women with a slower walking speed. Multiple linear regression analysis adjusted for age, BMI, grip strength, comorbidity, current smoking, and alcohol drinking status showed a significant association between faster self-reported walking speed and higher calcaneal stiffness index (p < 0.001). Conclusions: Our findings suggest that questionnaires of walking speed may be useful for predicting bone mass and that a fast self-reported walking may benefit bone health in postmenopausal women