Association of sirtuin 1 gene polymorphisms with nephrolithiasis in Eastern chinese population

Sirtuin 1 (SIRT1), an NAD(+)-dependent deacylase, has been identified to be associated with renal tubular inflammatory conditions and metabolic disorders, which are risk factors of nephrolithiasis. To further confirm the role of the SIRT1 in kidney stone formation, the expression of SIRT1 was analyzed based on a mouse model and the genetic polymorphisms of SIRT1 gene was compared between patients with kidney stones and controls. The calcium oxalate (CaOx) crystal-induced renal injury model was established to analyzed the expression of SIRT1 in the kidney tissue of both wild-type and ApoE(-/-) mice. And a total of 430 Eastern Chinese subjects (215 patients with nephrolithiasis and 215 age- and gender-matched controls) were recruited for the present study to investigate the associations between 6 common single nucleotide polymorphisms (SNPs) (i.e., rs10509291, rs3740051, rs932658, rs33957861, rs3818292 and rs1467568) in the SIRT1 gene and the incidence of kidney stones. Pairwise linkage disequilibrium and the haplotypes of the 6 SNPs were also analyzed. The genotypes of SIRT1 gene polymorphisms were analyzed by a Snapshot assay. Reduced expression of SIRT1 was observed in the kidney of the mice in the crystal group, revealing the potential role of SIRT1 in the nephrolithiasis. However, we did not find a significant association between the 6 SNPs of the SIRT1 gene and kidney stone formation in the Eastern Chinese population.

沉默信息调节因子1（SIRT1）是一种烟酰胺腺嘌呤二核苷酸（NAD⁺）依赖性脱酰基酶，已被确定与肾小管炎症状态和代谢紊乱相关，而这些都是肾结石的危险因素。为了进一步确认SIRT1在肾结石形成中的作用，基于小鼠模型分析了SIRT1的表达，并比较了肾结石患者和对照组之间SIRT1基因的遗传多态性。建立草酸钙（CaOx）晶体诱导的肾损伤模型，以分析野生型和载脂蛋白E基因敲除（ApoE⁻⁻）小鼠肾组织中SIRT1的表达。本研究共招募了430名中国东部受试者（215名肾结石患者和215名年龄及性别匹配的对照组），以研究SIRT1基因中的6个常见单核苷酸多态性（SNPs）（即rs10509291、rs3740051、rs932658、rs33957861、rs3818292和rs1467568）与肾结石发病率之间的关联。还分析了这6个SNPs的成对连锁不平衡和单倍型。通过Snapshot检测分析SIRT1基因多态性的基因型。在晶体组小鼠的肾脏中观察到SIRT1表达降低，揭示了SIRT1在肾结石形成中的潜在作用。然而，我们未发现SIRT1基因的6个SNPs与中国东部人群肾结石形成之间存在显著关联。