A 71-year-old man had been repeatedly admitted to our hospital with congestive heart failure, cerebral infarction and pneumonia. Under a diagnosis of mitral regurgitation and tricuspid regurgitation by echocardiography and catheter examination, mitral valve replacement and tricuspid annuloplasty were performed. Pathohistological study revealed a direct insertion of the papillary muscle into the anterior mitral leaflet (DPM) in addition to post-rheumatic valvular disease. These findings suggest that the increased rigidity of the scarring valve leaflets in combination with direct insertion of DPM lead to inadequate leaflet coaptation and apposition. This is the first report of mitral valve replacement for mitral regurgitation due to post-inflammatory valvular disease with DPM.

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.