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(SODS)一直被报道，其可能的原因已经被包括这个主要研究小组在内的几个小组研究。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)、湄公河附近等相当特殊的地区，因此最初对环境因素进行了强烈的猜测。虽然已经对饮食和社会习惯、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蕴含着遗传因素。从受害者家属那里获取了几份熟悉的血液样本，进行了与心脏病有关的基因分析，但没有得到阳性结果。此外，大多数病例在男性中发现，在女性中很少发现，这表明性激素可能起到了…的作用。更多的是泡在肥皂泡里。在男性中，常见的受害者是中年(20多岁至40多岁)的成年人，意外获得的血样中钾含量较低。肥皂主要发生在晚上的睡眠中，因为他们吃了大量碳水化合物的丰盛晚餐。综上所述，遗传和环境因素都应该被考虑在内。由于肥皂症的发病率似乎逐渐降低，因此受到的关注较少。这一事实可能强烈地暗示，营养的改善可能会改变肥皂水的发生率。因此，我们初步得出结论，肥皂症长期发生可能部分是由社会经济原因引起的。在过去十年中，在肥皂症发生频率较高的地区观察到尿结石的高发病率。虽然“真正的”肥皂水的病例很少被报道，但这个项目的目的是调查尿路结石和其他与肥皂水平行观察到的健康问题。在过去的四年里，科学研究补助金(A)(2)已经确定了大量的转运体，其中大多数似乎与肥皂水的健康问题有关。这一时期的一个亮点是确定和描述了尿酸盐转运体URAT1(SLC22中的一个新成员)。除了胱氨酸转运蛋白BAT1外，这个URAT1与重要的地理基因组特征密切相关，将从国内和国际两个方面进行研究。较少

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