SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values ,261025 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P=7.3361027 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P=1.7761029) and rs3781834 (P=1.0461028). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P=1.7161025) and rs744373 near BIN1 (P = 1.3961024). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations

Sympathetic overactivityを伴った重症破傷風の2例

破傷風は,Clostridium tetaniの産生毒素tetanospasminに起因する神経系疾患である.今日我が国では,予防接種の普及等により稀となった反面,軽微な外傷でも発症する本疾患は,外傷領域においては常に念頭に置くべき疾患である.その治療管理において痙攣,sympathetic overactivityに対する対処が重要となる.今回我々はsympathetic overactivityを伴った重症破傷風の2例を経験した.1例に対してはphenobartital,diazepam持続投与下の管理を約15日間要し,また他の1例はpancuronium bromide, midazolamを使用すると共に,循環動態安定のためfentanyl citrateを追加し,人工呼吸器管理期間は約28日を要した.いずれも軽快退院したものの,抗痙攣療法後の回復期に,筋力低下によるリハビリテーション,あるいはせん妄・自殺企図がみられ精神科的治療を要した.呼吸管理の進歩により生命予後は改善されたものの,抗痙攣療法後にも注意すべき合併症があり,全経過を通じ慎重な全身管理が必要である.Tetanus is a nervous system disease caused by tetanospasmin, a toxin produced by Clostridium tetani. In Japan, tetanus, which occurs in association with even a slight injury, should always be taken into consideration in the traumatology field, although there are rare cases of tetanus owing to the spread of vaccination, etc. Treatment of spasm and sympathetic overactivity plays an important role in the therapeutic control of this disease. We had an experience of treating two patients suffering from severe tetanus with sympathetic overactivity. For one patient, it took about 15 days to control the disease by continuous administration of phenobartital and diazepam. For the other patient, pancuronium bromide and midazolam were used and fentanyl citrate was added for circulatory dynamic stabilization, and control with a ventilator required about 28 days. Although both patients were cured from the tetanus and discharged, reduced myodynamia required rehabilitation, and delirium and suicide attempts required psychiatric treatment during the recovery period following the anti-spasm therapy. Careful systemic control of tetanus patients is necessary throughout the course of disease as complications to be watched may occur following the anti-spasm therapy as well, although the progress in respiratory control has contributed to the improvement in prognosis of tetanus patients