PDF(Pubmed)
Abstract：
Sickle cell nephropathy (SCN) is a common complication of sickle cell disease (SCD) that significantly contributes to morbidity and mortality. In addition to clinical and life-style factors, genetic variants influence this risk. We performed a systematic review, searching five databases. Studies evaluating the effect of genetic modifiers on SCN were eligible. Twenty-eight studies (fair-to-good quality) were included: one genome-wide association study, twenty-six case-control studies, and one article combining both approaches. APOL1 was significantly associated with albuminuria and hyperfiltration in children and with worse glomerular filtration in adults. On the other hand, alpha-thalassemia protected patients against albuminuria and hyperfiltration, while BCL11A variants were protective against albuminuria alone. The HMOX1 long GT-tandem repeat polymorphism led to a lower glomerular filtration rate. No modifiers for the risk of hyposthenuria were identified. A genome-wide association approach identified three new loci for proteinuria (CRYL1, VWF, and ADAMTS7) and nine loci were linked with eGFR (PKD1L2, TOR2A, CUBN, AGGF1, CYP4B1, CD163, LRP1B, linc02288, and FPGT-TNNI3K/TNNI3K). In conclusion, this systematic review supports the role of genetic modifiers in influencing the risk and progression of SCN. Incorporating and expanding this knowledge is crucial to improving the management and clinical outcomes of patients at risk.
摘要：
镰状细胞肾病（SCN）是镰状细胞病（SCD）的常见并发症，显着导致发病率和死亡率。除了临床和生活方式因素，遗传变异会影响这种风险。我们进行了系统的审查,搜索五个数据库。评估遗传修饰剂对SCN的影响的研究合格。包括28项研究（质量从一般到良好）：一项全基因组关联研究，26项病例对照研究,一篇文章结合了两种方法。APOL1与儿童的蛋白尿和过度滤过显着相关，而成人的肾小球滤过率较差。另一方面,α-地中海贫血保护患者免受蛋白尿和超滤，而BCL11A变体单独对蛋白尿具有保护作用。HMOX1长GT串联重复多态性导致较低的肾小球滤过率。没有鉴定出神经尿过少风险的调节剂。全基因组关联方法确定了蛋白尿的三个新基因座（CRYL1，VWF，和ADAMTS7）和9个基因座与eGFR（PKD1L2，TOR2A，CUBN,AGGF1,CYP4B1,CD163,LRP1B,linc02288和FPGT-TNNI3K/TNNI3K)。总之,本系统综述支持遗传修饰因子在影响SCN风险和进展中的作用.整合和扩展这些知识对于改善有风险患者的管理和临床结果至关重要。
