Genetic Abnormality of Renal Proximal Tubule-Specific Transporters as Causes of Sudden Death Syndrome in South-Eastern Asia

长期以来，不明原因猝死综合征（SUDS）一直有报道，包括本首席研究员团队在内的几个小组一直在寻找其可能的原因。主要的可能性被认为是遗传或环境因素。由于受害者来自泰国东北部（E-san），湄公河附近地区等非常特殊的地区，因此最初强烈推测环境因素。尽管人们对饮食和社会习惯、食物成分、饮用水、土壤等进行了广泛的分析，但尚未确定明确的结果。同一家庭中多名受害者的高发生率暗示了遗传致病因素。从受害者家庭成员中提取了几个熟悉的血液样本进行与心脏病有关的遗传分析，但没有得到阳性结果。此外，男性多见，女性少见，提示性激素可能起作用 ...更多信息 在SUDS。在男性中，通常的受害者是中年人（20 - 40岁），意外获得的血液样本含有低钾浓度。SUDS多发生在夜间进食含大量碳水化合物的晚餐后的睡眠中。遗传因素和环境因素是综合考虑的重要因素，但SUDS的发病率呈逐渐下降趋势，因此对SUDS的研究较少。这一事实可能强烈暗示营养的改善可能会改变SUDS的发病率。因此，我们初步得出结论，SUDS发生了很长一段时间可能会导致根据部分社会经济reason.During以前的努力，以确定SUDS的原因在过去的十年中，泌尿系结石的发病率高，已观察到在该地区的SUDS发生率高。虽然“真实的”SUDS病例很少报道，但该项目旨在调查泌尿系统结石等与SUDS平行观察到的健康问题。在过去的四年中，科学研究补助金（A）（2）对大量转运者进行了表征，其中大部分转运者似乎与SUDS的健康问题有关。这一时期的一个亮点是确定和表征尿酸盐转运蛋白URAT 1（SLC 22的新成员）。除了胱氨酸转运蛋白BAT 1外，URAT 1还与地理上重要的基因组特征密切相关，国内外都有研究。少

Since a long time, sudden unexplained death syndrome (SUDS) has been reported, and its possible causes have been pursued by several groups including this principal investigator's team. The major possibilities were assumed to be either genetic or environmental factors. Since the victims have been originated from quite special area like North-eastern Part of Thailand (E-san), district near Mekong River etc, environmental factors were at first speculated strongly. Although eating and social habits, food constituents, drinking water, soil etc have been extensively analyzed, no clear-cut results have been identified yet.The high incidence of plural victims within same families implied genetic causative factors. Several familiar blood samples from victim's family members were obtained for genetic analyses relating with heart diseases, however, no positive findings were gotten. In addition, most cases were found in males and seldom found in females suggesting that sex hormone might play a rol … More e in SUDS. Within male gender, usual victims were adults of middle ages (20s-40s), and accidentally obtained blood samples contained low potassium concentrations. SUDS occurred mostly at night during sleep after eating heavy dinners with much carbohydrate. Taken together, both genetic and environmental factors should be taken into account.Since SUDS incidence seemed to become gradually lower, less attention has been made. This fact may imply strongly a nutritious improvement might change the incidence of SUDS. Thus, we tentatively conclude that the SUDS occurred for a long time might cause according in part to a socio-economical reason.During previous efforts to identify causes of SUDS in the last decade, high incidence of urinary stones has been observed in the area where SUDS occurred at high rates. Although cases of "real" SUDS have been seldom reported, health problems like urinary stones and others observed in parallel with SUDS have been aimed to investigate in this project.During past four years by the Grant-in-Aid for Scientific Research (A)(2), tremendously large numbers of transporters most of which seem to be related with the health problems in SUDS have been characterized. A highlight of this period was to identify and characterize urate transporter, URAT1 (a new member in SLC22). In addition to cystine transporter, BAT1, this URAT1 was tightly related with geographically important genomic characteristics to be investigated from both domestic and international aspects. Less