Genome-wide association studies have identified various genetic variants associated with complex disorders. However, these studies have commonly been conducted in a cross-sectional manner. Therefore, we performed a longitudinal exome-wide association study (EWAS) in a Japanese cohort. We aimed to identify genetic variants that confer susceptibility to hypertension using ~244 000 single-nucleotide variants (SNVs) and physiological data from 6026 Japanese individuals who underwent annual health check-ups for several years. After quality control, the association of hypertension with SNVs was tested using a generalized estimating equation model. Finally, our longitudinal EWAS detected seven hypertension-related SNVs that passed strict criteria. Among these variants, six SNVs were densely located at 12q24.1, and an East Asian-specific motif (haplotype) ‘CAAAA’ comprising five derived alleles was identified. Statistical analyses showed that the prevalence of hypertension in individuals with the East Asian-specific haplotype was significantly lower than that in individuals with the common haplotype ‘TGGGT’. Furthermore, individuals with the East Asian haplotype may be less susceptible to the adverse effects of smoking on hypertension. The longitudinal EWAS for the recessive model showed that a novel SNV, rs11917356 of COL6A5, was significantly associated with systolic blood pressure, and the derived allele at the SNV may have spread throughout East Asia in recent evolutionary time.

Heat shock proteins (Hsps) are generally known to be induced in response to a range of stressful stimuli such as hyperthermia, immobilization, UV radiation, arsenite, various chemicals, and drugs. In addition, these proteins have been suggested to have roles in protecting cells against apoptotic cell death. The ataxic mutant Pogo (pogo/pogo) mouse is a novel neurological ataxic mutant, which is derived from Korean wild type mouse (KJR/Mskist) strain. Pogo mutation is considered as an alleles of alpha subunit of P/Q-type calcium channel mutants such as rolling mouse Nagoya (RMN), tottering, and leaner. We investigated the topographical Hsp25 expression using immunohistochemistry and western blot analysis in several ataxic mutant mice: RMN, tottering, leaner, Pogo and Korean wild mouse. In the cerebellum of the RMN, tottering, leaner, and normal mouse including Balb/C, C57BL/6 and ICR mouse, Hsp25 was expressed in a subset of Purkinje cells that form parasagittal stripes. The Hsp25 expression is largely restricted to specific cerebellar lobules: VI /VII (the central zone: CZ), and IX/X (the nodular zone: NZ). Surprisingly, no Hsp25-immunoreactive Purkinje cells were seen in CZ and NZ of the cerebellum of Pogo (pogo/pogo), heterozygotes Pogo (pogo/+), and Korean wild mouse. Moreover, in western blot analysis, there was no cerebellar Hsp25 expression in ataxic Pogo mouse including Korean wild mouse. These data suggest that cerebellar Hsp25 expression was irrelevant with the development of ataxia in Pogo mouse.
Alleles ; Animals ; Arsenites ; Ataxia ; Blotting, Western ; Calcium Channels ; Cell Death ; Cerebellum ; Fever ; Heat-Shock Proteins ; Heterozygote ; Hot Temperature ; Immobilization ; Immunohistochemistry ; Mice ; Mice, Inbred ICR ; Proteins ; Purkinje Cells ; Sprains and Strains

Colorectal endoscopic submucosal dissection (ESD) is now a well-established endoscopic treatment for early-stage colorectal neoplasms, especially in Asian countries, including Japan. Despite the spread of colorectal ESD, there are still situations in which achieving successful submucosal dissection is difficult. Various novel techniques and devices have been developed to overcome these difficulties, and past reports have shown that some of these strategies can be applied to colorectal ESD. We review several recent developments in the field. The techniques reviewed include the pocket creation method and traction methods and the devices reviewed include the overtube with balloon and electrosurgical knives with water-jet function. These improved techniques and devices can facilitate safer, more reliable ESDs and expand its applicability and acceptability all over the world.
Asian Continental Ancestry Group ; Colorectal Neoplasms ; Humans ; Japan ; Methods ; Traction

BACKGROUND: Most studies have reported that suicide mortality rates are negatively associated with lithium levels in tap water; however, a few studies showed either no association or a positive association. Thus, the association between suicide mortality and lithium levels in tap water remains controversial. To clarify the association, our study evaluated the association between lithium levels in tap water and suicide mortality rates in Miyazaki Prefecture of Japan, after adjusting for confounding factors. METHODS: We measured lithium levels in tap water across the 26 municipalities of Miyazaki Prefecture in Japan. We examined the standardized mortality ratio (SMR) for suicide in each municipality and used the data as the average suicide SMRs over 5 years (2009-2013). Weighted least-squares regression analysis, adjusted for the size of each municipality's population, was used to investigate the association between lithium levels in tap water and suicide SMRs. In addition to a crude model, in an adjusted model, potential confounding factors (proportion of elderly people, proportion of one-person households, annual marriage rate, annual mean income, unemployment rate, the density of medical doctors per 100,000 people, annual total rainfall, and proportion of people with a college education or higher) were added as covariates. RESULTS: We showed that male and female suicide SMRs were not associated with lithium levels in tap water in Miyazaki Prefecture. After adjusting for confounders, male suicide SMRs were significantly and positively associated with the proportion of elderly people in the population and annual total rainfall, and female suicide SMRs were associated with the proportion of elderly people in the population. CONCLUSIONS No association between lithium levels in tap water and suicide mortality rates was found in Miyazaki Prefecture.
Drinking Water ; analysis ; Female ; Humans ; Japan ; Lithium ; analysis ; Male ; Suicide ; statistics & numerical data