Ware Erin B, Smith Jennifer A, Zhao Wei, Ganesvoort Ron T, Curhan Gary C, Pollak Martin, Mount David B, Turner Stephen T, Chen Guotao, Shah Ronak Jagdeep, Kardia Sharon L R, Lieske John C
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor.
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor.
Mayo Clin Proc Innov Qual Outcomes. 2019 Nov 22;3(4):448-460. doi: 10.1016/j.mayocpiqo.2019.08.007. eCollection 2019 Dec.
The urinary excretion of organic and inorganic substances and their concentrations have attracted extensive attention for their role in the pathogenesis of urinary stone disease. The urinary excretion of specific factors associates with sex and age and seems to have a hereditary component, but the precise genomic determinants remain ill-defined.
Genome-wide association studies previously conducted in 3 cohorts (Genetic Epidemiology Network of Arteriopathy study, January 1, 2006, through December 31, 2012; the combined Nurses' Health Study (NHS), NHS II, and Health Professionals Follow-up Study, January 1, 1994, through December 31, 2003; and the Prevention of Renal and Vascular End-stage Disease study, January 1, 1997, through December 31, 1998) were combined into meta-analyses to evaluate genetic associations with available urinary phenotypes relevant to stone pathogenesis (calcium, magnesium, and uric acid excretion; total urine volume).
One region on chromosome 9q21.13 showed strong evidence of an association with urinary magnesium excretion. The strongest signal in this region was near , whose protein product mediates magnesium transport in the colon and kidney, and , , , and (rs1176815; 1.70×10, with each copy of the A allele corresponding to a daily 5.29-mg decrease in magnesium excretion). The single nucleotide polymorphism (SNP) that achieved genome-wide significance for calcium excretion (rs17216707 on chromosome 20; 1.12×10) was previously associated with fibroblast growth factor 23 levels, which regulate phosphorus and vitamin D metabolism. Urine volume and uric acid excretion did not have any genome-wide significant SNPs.
Common variants near genes important for magnesium metabolism and bone health associate with urinary magnesium and calcium excretion.
有机和无机物质的尿排泄及其浓度因其在尿路结石病发病机制中的作用而受到广泛关注。特定因素的尿排泄与性别和年龄相关，似乎具有遗传成分，但确切的基因组决定因素仍不明确。
以前在3个队列中进行的全基因组关联研究（动脉病遗传流行病学网络研究，2006年1月1日至2012年12月31日；护士健康研究（NHS）、NHS II和卫生专业人员随访研究的合并队列，1994年1月1日至2003年12月31日；以及预防肾脏和血管终末期疾病研究，1997年1月1日至1998年12月31日）被合并进行荟萃分析，以评估与尿路结石发病机制相关的可用尿表型（钙、镁和尿酸排泄；总尿量）的遗传关联。
9号染色体q21.13上的一个区域显示出与尿镁排泄相关的有力证据。该区域最强的信号位于 附近，其蛋白质产物介导结肠和肾脏中的镁转运，以及 、 、 和 （rs1176815；1.70×10，A等位基因的每个拷贝对应于每日镁排泄量减少5.29毫克）。对钙排泄达到全基因组显著性的单核苷酸多态性（SNP）（20号染色体上的rs17216707；1.12×10）先前与成纤维细胞生长因子23水平相关，该因子调节磷和维生素D代谢。尿量和尿酸排泄没有任何全基因组显著性的SNP。
对镁代谢和骨骼健康重要的基因附近的常见变异与尿镁和钙排泄相关。
