Impact of long-hours family caregiving on non-fatal coronary heart disease risk in middle-aged people: Results from a longitudinal nationwide survey in Japan

AimThe effects of family caregiving, especially long-hours caregiving, on coronary heart disease (CHD) are debatable. We examined the impact of family caregiving on incident non-fatal CHD.MethodsWe used data from the Longitudinal Survey of Middle-Aged and Elderly Persons from 2005 to 2010, a nationwide panel survey for Japanese people aged 50–59 years in 2005 (baseline). After we excluded non-respondents and people with missing key variables at baseline, 25 121 individuals without CHD, stroke or cancer were followed up for a mean of 4.6 years. The exposure was assessed at baseline by three indicators: (i) family caregiving; (ii) hours spent caregiving; and (iii) kinship type of care recipient. The non-fatal CHD incidence was identified according to questionnaire responses from 2006 to 2010.ResultsCox\u27s proportional hazards analysis did not show a statistically significant association between family caregiving and incident non-fatal CHD (hazard ratio [HR] 1.13, 95% confidence interval [CI] 0.92–1.40). Caregivers who spent 20–69 h per week on care showed a statistically significant increased risk for non-fatal CHD (HR 1.78, 95% CI 1.23–2.58) compared with non-caregivers; whereas this increased risk was statistically significant only among women (HR 1.98, 95% CI 1.27–3.08), but not among men (HR 1.35, 95% CI 0.67–2.71). Kinship type of care recipient did not make a significant difference to the effects of family caregiving on incident non-fatal CHD.ConclusionsLong-hours family caregiving could be an independent risk factor for incident non-fatal CHD among middle-aged women in Japan. Geriatr Gerontol Int 2017; 17: 2109–2115

Sovereign Credit Risk, Liquidity and ECB Intervention: Deus Ex Machina?

This paper explores the interaction between credit risk and liquidity, in the context of the inter-vention by the European Central Bank (ECB), during the Euro-zone crisis. The laboratory for our investigation is the Italian sovereign bond market, the largest in the Euro-zone. We use a unique data set obtained from the Mercato dei Titoli di Stato (MTS), which provides tick-by-tick trade and quote data from individual broker-dealers. Our database covers the sovereign bonds of most European-zone countries, for the period June 1, 2011 to December 31, 2012, which includes much of the Euro-zone crisis period. We document a strong and dynamic relationship between changes in Italian sovereign credit risk and liquidity in the secondary bond market, conditional on the level of credit risk, measured by the Italian sovereign credit default swap (CDS) spread. We demonstrate the existence of a threshold of 500 basis points (bp) in the CDS spread, above which there is a structural change in this relationship. Other global systemic factors also affect market liquidity, but the specific credit risk of primary dealers plays only a modest role in affecting market liquidity, especially under conditions of stress. Moreover, the data indicate that there is a clear structural break following the announcemen

Low-Dose and Long-Term 14-Member Macrolide Therapy for Palomoplantar Pustulosis

We investigated the clinical efficacy of low-dose and long-term 14-member macrolide therapy for 33 patients with Palomoplantar Pustulosis (PPP) most of whom showed a poor clinical response to topical corticosteroid and/or photo chemotherapy. After 4-12 weeks treatment with oral erythromycin (EM; 600mg/day) or clarithromycin (CAM ; 200 mg/day) in combination with previously used corticosteroid ointment, clinical evaluation was made on the basis of clinical score. Results are as follows: marked improvement ; 19 patients (57.6%), moderate improvement ; 7 patients, no clinical response ; 7 patients. There was no serious side effect during the observation period. In vitro studies suggest that CAM, a 14-member macrolide, significantly down-regulated IL-8 production by keratinocytes stimulated with combination of IFNﾎｳ and TNFﾎｱ or staphylococcal-superantigen(SEB)and IFNﾎｳ both at protein and mRNA levels. We would like to propose that low-dose and long-term 14-member macrolide therapy is effective and an alternate therapy for PPP with poor response to ordinal dermatological therapy of which mechanism is presumable inhibition of neutrophil chemotaxisis by inhibiting IL-8 production by keratinocytes

Identification of TNFSF13, SPATC1L, SLC22A25 and SALL4 as novel susceptibility loci for atrial fibrillation by an exome‑wide association study

An exome‑wide association study (EWAS) was performed to identify genetic variants, particularly low‑frequency or rare coding variants with a moderate to large effect size, that confer susceptibility to atrial fibrillation in Japanese. The EWAS for atrial fibrillation was performed with 13,166 subjects (884 patients with atrial fibrillation and 12,282 controls) using an Illumina HumanExome‑12 DNA Analysis BeadChip or Infinium Exome‑24 BeadChip arrays. The association of atrial fibrillation with allele frequencies of 41,243 single nucleotide polymorphisms (SNPs) that passed quality control was examined with Fisher\u27s exact test. Based on Bonferroni\u27s correction, a P<1.21x10‑6 was considered statistically significant. The EWAS for atrial fibrillation revealed that 122 SNPs were significantly associated with this condition. The association of the identified SNPs to atrial fibrillation was further examined by multivariable logistic regression analysis with adjustment for age, sex and the prevalence of hypertension. Eight SNPs were related (P<0.01) to atrial fibrillation, among which three polymorphisms, rs11552708 [G/A (G67R)]of TNF superfamily member 13 (TNFSF13; dominant model; P=9.36x10‑9; odds ratio, 0.58), rs113710653 [C/T (E231 K)] of spermatogenesis and centriole associated 1 like (SPATC1L; dominant model; P=1.09x10‑5; odds ratio, 3.27), and rs11231397 [G/C (R300T)] of solute carrier family 22 member 25 (SLC22A25; additive model; P=3.71x10‑5; odds ratio, 1.77), were significantly (P<1.02x10‑4) associated with this condition. The minor T allele of rs113710653 and the minor C allele of rs11231397 were risk factors for atrial fibrillation, whereas the minor A allele of rs11552708 was protective against this condition. In addition, rs77538589 [C/T (G117R)] of SALL4 exhibited a tendency to be associated with atrial fibrillation (dominant model; P=0.0002; odds ratio, 1.88), with the minor T allele representing a risk factor for this condition. TNFSF13, SPATC1L, SLC22A25 and SALL4 may thus be novel susceptibility loci for atrial fibrillation in the Japanese population

Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies

Impact of the HCRTR2 gene risk variant on schizotypal personality traits (mean ± SD). (DOC 54 kb

Identification of eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies

We have performed exome-wide association studies to identify single nucleotide polymorphisms that influence serum concentrations of triglycerides, high density lipoprotein (HDL)–cholesterol, or low density lipoprotein (LDL)–cholesterol or confer susceptibility to hypertriglyceridemia, hypo–HDL-cholesterolemia, or hyper–LDL-cholesterolemia in Japanese. Exome-wide association studies for serum triglycerides (13,414 subjects), HDL-cholesterol (14,119 subjects), LDL-cholesterol (13,577 subjects), hypertriglyceridemia (4742 cases, 8672 controls), hypo–HDL-cholesterolemia (2646 cases, 11,473 controls), and hyper–LDL-cholesterolemia (4489 cases, 9088 controls) were performed with HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. Twenty-four, 69, or 32 loci were significantly (P < 1.21 × 10–6) associated with serum triglycerides, HDL-cholesterol, or LDL-cholesterol, respectively, with 13, 16, or 9 of these loci having previously been associated with triglyceride-, HDL-cholesterol–, or LDL-cholesterol–related traits, respectively. Two single nucleotide polymorphisms (rs10790162, rs7350481) were significantly related to both serum triglycerides and hypertriglyceridemia; three polymorphisms (rs146515657, rs147317864, rs12229654) were significantly related to both serum HDL-cholesterol and hypo–HDL-cholesterolemia; and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) were significantly related to both serum LDL-cholesterol and hyper–LDL-cholesterolemia. Among polymorphisms identified in the present study, two polymorphisms (rs146515657, rs147317864) may be novel determinants of hypo–HDL-cholesterolemia, and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) may be new determinants of hyper–LDL-cholesterolemia. In addition, 12, 61, 23, or 3 polymorphisms may be new determinants of the serum triglyceride, HDL-cholesterol, or LDL-cholesterol concentrations or of hyper–LDL-cholesterolemia, respectively

Identification of STXBP2 as a novel susceptibility locus for myocardial infarction in Japanese individuals by an exome-wide association study

We performed exome-wide association studies to identify genetic variants—in particular, low-frequency variants with a large effect size—that confer susceptibility to coronary artery disease or myocardial infarction in Japanese. The exome-wide association studies were performed with 12,698 individuals (3488 subjects with coronary artery disease including 2438 with myocardial infarction, 9210 controls) and with the use of the Illumina HumanExome-12 DNA Analysis or Infinium Exome-24 BeadChip. The relation of allele frequencies for 41,339 single nucleotide polymorphisms that passed quality control to coronary artery disease or myocardial infarction was examined with Fisher’s exact test. The exome-wide association study for coronary artery disease revealed that 126 single nucleotide polymorphisms were significantly (P <1.21 × 10–6) associated with this condition. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of hypertension, diabetes mellitus, and dyslipidemia showed that six of these polymorphisms were related (P < 0.01) to coronary artery disease, but none was significantly (P < 9.92 × 10–5) associated with this condition. The exome-wide association study for myocardial infarction revealed that 114 single nucleotide polymorphisms were significantly (P <1.21 × 10–6) associated with this condition. Multivariable logistic regression analysis with adjustment for covariates revealed that nine of these polymorphisms were related (P < 0.01) to myocardial infarction. Among these nine polymorphisms, rs188212047 [G/T (L212F)] of STXBP2 was significantly (dominant model; P = 4.84 × 10–8; odds ratio, 2.94) associated with myocardial infarction. STXBP2 may thus be a novel susceptibility locus for myocardial infarction in Japanese

Identification of rs7350481 at chromosome 11q23.3 as a novel susceptibility locus for metabolic syndrome in Japanese individuals by an exome-wide association study

We have performed exome-wide association studies to identify genetic variants that influence body mass index or confer susceptibility to obesity or metabolic syndrome in Japanese. The exome-wide association study for body mass index included 12,890 subjects, and those for obesity and metabolic syndrome included 12,968 subjects (3954 individuals with obesity, 9014 controls) and 6817 subjects (3998 individuals with MetS, 2819 controls), respectively. Exome-wide association studies were performed with Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of genotypes of single nucleotide polymorphisms to body mass index was examined by linear regression analysis, and that of allele frequencies of single nucleotide polymorphisms to obesity or metabolic syndrome was evaluated with Fisher’s exact test. The exome-wide association studies identified six, 11, and 40 single nucleotide polymorphisms as being significantly associated with body mass index, obesity (P <1.21 × 10–6), or metabolic syndrome (P <1.20 × 10–6), respectively. Subsequent multivariable logistic regression analysis with adjustment for age and sex revealed that three and five single nucleotide polymorphisms were related (P < 0.05) to obesity or metabolic syndrome, respectively, with one of these latter polymorphisms—rs7350481 (C/T) at chromosome 11q23.3—also being significantly (P < 3.13 × 10–4) associated with metabolic syndrome. The polymorphism rs7350481 may thus be a novel susceptibility locus for metabolic syndrome in Japanese. In addition, single nucleotide polymorphisms in three genes (CROT, TSC1, RIN3) and at four loci (ANKK1, ZNF804B, CSRNP3, 17p11.2) were implicated as candidate determinants of obesity and metabolic syndrome, respectively