Association between Milk Intake and Incident Stroke among Japanese Community Dwellers: The Iwate-KENCO Study

We aimed to evaluate the association between the milk consumption and incident stroke in a Japanese population, where milk consumption is lower than that of Western countries. In total, 14,121 participants (4253 men and 9868 women) aged 40–69 years, free from cardiovascular diseases (CVD) were prospectively followed for 10.7 years. Participants were categorized into four groups according to the milk intake frequency obtained from a brief-type self-administered diet questionnaire. The adjusted HRs of total stroke, ischemic stroke and haemorrhagic stroke associated with milk intake frequency were calculated using the Cox proportional hazards model. During the follow-up, 478 stroke cases were detected (208 men and 270 women). Compared to women with a milk intake of <2 cups/week, those with an intake of 7 to <12 cups/week had a significantly low risk of ischemic stroke in a model adjusting CVD risk factors; the HR (95% CI) was 0.53 (0.32–0.88). No significant associations were found in men. This study suggested that milk intake of 7 to <12 cups/week decreased the risk of ischemic stroke in Japanese women. Milk intake of about 1 to <2 cups/day may be effective in the primary prevention of ischemic stroke in a population with low milk intake

Mutations in POLR3A and POLR3B Encoding RNA Polymerase III Subunits Cause an Autosomal-Recessive Hypomyelinating Leukoencephalopathy

Congenital hypomyelinating disorders are a heterogeneous group of inherited leukoencephalopathies characterized by abnormal myelin formation. We have recently reported a hypomyelinating syndrome characterized by diffuse cerebral hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC). We performed whole-exome sequencing of three unrelated individuals with HCAHC and identified compound heterozygous mutations in POLR3B in two individuals. The mutations include a nonsense mutation, a splice-site mutation, and two missense mutations at evolutionally conserved amino acids. Using reverse transcription-PCR and sequencing, we demonstrated that the splice-site mutation caused deletion of exon 18 from POLR3B mRNA and that the transcript harboring the nonsense mutation underwent nonsense-mediated mRNA decay. We also identified compound heterozygous missense mutations in POLR3A in the remaining individual. POLR3A and POLR3B encode the largest and second largest subunits of RNA Polymerase III (Pol III), RPC1 and RPC2, respectively. RPC1 and RPC2 together form the active center of the polymerase and contribute to the catalytic activity of the polymerase. Pol III is involved in the transcription of small noncoding RNAs, such as 5S ribosomal RNA and all transfer RNAs (tRNA). We hypothesize that perturbation of Pol III target transcription, especially of tRNAs, could be a common pathological mechanism underlying POLR3A and POLR3B mutations