Longitudinal exome-wide association study to identify genetic susceptibility loci for hypertension in a Japanese population

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.

A Case of Rheumatoid Pleurisy Detected from Multilocular Pleural Effusion Mimicking Empyema / 日本農村医学会雑誌

　　Thoracoscopic pleural biopsy is useful when other investigations have not revealed the cause of pleural effusion. We report here a case of rheumatoid pleurisy detected from multilocular pleural effusion mimicking empyema. A 65-year-old man visited our hospital for cough persisting for 1 month and arthralgia for 3 days. He was diagnosed with rheumatoid arthritis after a routine checkup. He had an exudative multilocular pleural effusion with negative cultures. Antibiotic therapy was not effective, and thoracic drainage was not successful because of the multilocular pleural effusion. We then performed diagnostic and therapeutic thoracoscopic pleural decortication. Pathological examination of parietal pleural biopsy specimens revealed only non-specific inflammatory changes. Based on histological and clinical findings, we suspected rheumatoid pleurisy and administered empirical steroid therapy. This therapy produced a complete response and thus the diagnosis of rheumatoid pleurisy was established.