V-ATP酶相关基因变异致遗传性远端肾小管酸中毒的分子遗传学研究进展  

Research progress on inherited distal renal tubular acidosis due to variants of V-ATPase-related genes

作　　者：彭思琪 伍倩倩 杨钧岚 王彬 张晓良[1] Peng Siqi;Wu Qianqian;Yang Junlan;Wang Bin;Zhang Xiaoliang(Institute of Nephrology,Department of Nephrology,Zhongda Hospital of Southeast University,Nanjing,Jiangsu 210009,China)

机构地区：[1]东南大学肾脏病研究所,东南大学附属中大医院肾脏科,南京210009

出　　处：《中华医学遗传学杂志》2024年第11期1399-1404,共6页Chinese Journal of Medical Genetics

基　　金：江苏省重点研发计划社会发展项目(BE2021737、BE2023770)。

摘　　要：V-ATP酶(V-ATPase)是一类通过水解ATP获取能量并介导H+跨膜转运的膜锚定蛋白复合体,其通过对细胞内外多种结构的酸化作用调控一系列重要的生命活动。V-ATPase相关基因发生致病性变异可抑制其酶活性,降低肾小管A型闰细胞将H+泵入管腔的能力,最终导致常染色体隐性遗传性远端肾小管酸中毒(dRTA)。随着分子生物学诊断技术的发展,现已明确ATP6V1B1和ATP6V0A4是dRTA的致病基因;此外,有研究在动物/细胞水平揭示ATP6V1C2和ATP6V1G3基因致病性变异可能与dRTA相关,但缺乏相关临床证据。本文就V-ATPase相关基因变异致dRTA的分子作用机制相关研究进展作详细综述,以期为临床诊断和药物开发提供参考。V-ATPases are a class of multi-subunit protein complexes that utilize energy derived from ATP hydrolysis for mediating H+transport across cell membranes,which plays an important role in a range of life activities by acidifying the intracellular and extracellular environment.Variants of V-ATPase genes may lead to complete or partial loss of V-ATPase activity,which in turn may impair the ability of type A intercalated cells in renal tubules to pump H+into the tubular lumen,ultimately resulting in the onset of autosomal recessive distal renal tubular acidosis(dRTA).With the rapid development of molecular techniques,ATP6V0A4 and ATP6V1B1 have now been identified as the pathogenic genes for dRTA.Moreover,animal and cell experiments have substantiated the implication of V-ATPase subunit genes including ATP6V1C2 and ATP6V1G3 in the development of dRTA,though clinical evidence is still limited.This article has reviewed recent progress on the genetic and molecular mechanisms of V-ATPase subunit gene variants which can lead to dRTA,which may shed light on the diagnosis and treatment of this disease.

关 键 词：V-ATP酶 基因变异 遗传性远端肾小管酸中毒 分子机制 

分 类 号：R692.6[医药卫生—泌尿科学]