Molecular Genetics of Kidney Stone Disease

Kidney stone disease (KSD) is a multifactorial disease caused by a complex interaction of genetic and environmental factors. It causes significant morbidity and medical care expenses worldwide, which can be found commonly in tropical territory including Thailand. A majority of kidney stones are composed of calcium and it is usually associated with a metabolic abnormality such as hypercalciurea, hyperoxaurea, hyperphosphaturia, hyperuricosuria, hypocitraturea, and a defect of urinary acidification. However, few defects associated with monogenic forms of KSD have been identified. To date, molecular genetic studies to investigate genetic contribution of multifactorial KSD have been extensively performed and a number of causative genes have been recognized, but they vary among populations. In Thailand, the highest prevalence of KSD was observed in the Northeastern (NE) area. Its etiology and pathogenesis are still obscure and unique characteristics with no conditions of increased urinary solutes such as hypercalciurea, hyperoxaurea, and hyperuricosuria that are different from what has been reported in other ethnic groups are shown. The study to identify causative genes will provide more understanding of pathogenesis underlying KSD and also the unique pathogenesis of KSD in NE Thai patients. These will lead to improved quality and efficiency of patient care, diagnosis, prevention and control of diseases and complications. The knowledge of reported monogenic and multifactorial KSD, and the update on molecular genetic studies to investigate genes responsible for the disease in NE Thai patients are reviewed in this article.