Li Nan, Gu Harvest F
Department of Endocrinology, Jiangsu Province Hospital of Traditional Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
Front Genet. 2022 May 3;13:799224. doi: 10.3389/fgene.2022.799224. eCollection 2022.
The (Solute carrier family 12 member 3) gene encodes a sodium-chloride cotransporter and mediates Na and Cl reabsorption in the distal convoluted tubule of kidneys. An experimental study has previously showed that with knockdown of zebrafish ortholog, slc12a3 led to structural abnormality of kidney pronephric distal duct at 1-cell stage, suggesting that may have genetic effects in renal disorders. Many clinical reports have demonstrated that the function-loss mutations in the gene, mainly including Thr60Met, Asp486Asn, Gly741Arg, Leu859Pro, Arg861Cys, Arg913Gln, Arg928Cys and Cys994Tyr, play the pathogenic effects in Gitelman syndrome. This kidney disease is inherited as an autosomal recessive trait. In addition, several population genetic association studies have indicated that the single nucleotide variant Arg913Gln in the gene is associated with diabetic kidney disease in type 2 diabetes subjects. In this review, we first summarized bioinformatics of the gene and its genetic variation. We then described the different genetic and biological effects of in Gitelman syndrome and diabetic kidney disease. We also discussed about further genetic and biological analyses of as pharmacokinetic targets of diuretics.
（溶质载体家族12成员3）基因编码一种氯化钠共转运体，并介导肾脏远曲小管中钠和氯的重吸收。先前的一项实验研究表明，敲低斑马鱼直系同源基因slc12a3会导致1细胞期肾脏前肾远曲小管的结构异常，这表明该基因可能在肾脏疾病中具有遗传效应。许多临床报告表明，该基因的功能丧失突变，主要包括Thr60Met、Asp486Asn、Gly741Arg、Leu859Pro、Arg861Cys、Arg913Gln、Arg928Cys和Cys994Tyr，在吉特曼综合征中起致病作用。这种肾脏疾病以常染色体隐性性状遗传。此外，几项群体遗传关联研究表明，该基因中的单核苷酸变体Arg913Gln与2型糖尿病患者的糖尿病肾病有关。在这篇综述中，我们首先总结了该基因及其遗传变异的生物信息学。然后，我们描述了该基因在吉特曼综合征和糖尿病肾病中的不同遗传和生物学效应。我们还讨论了该基因作为利尿剂药代动力学靶点的进一步遗传和生物学分析。
