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

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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