常见基因变异对儿童肾脏结局的影响。
Influence of common genetic variants on childhood kidney outcomes.
作者信息
Miliku Kozeta, Vogelezang Suzanne, Franco Oscar H, Hofman Albert, Jaddoe Vincent W V, Felix Janine F
机构信息
The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
出版信息
Pediatr Res. 2016 Jul;80(1):60-6. doi: 10.1038/pr.2016.44. Epub 2016 Mar 9.
BACKGROUND
Kidney measures in early life are associated with kidney disease in later life. We hypothesized that these associations are partly explained by common genetic variants that lead to both smaller kidneys with lower kidney function in early childhood and kidney disease in adulthood.
METHODS
We examined in a population-based prospective cohort study among 4,119 children the associations of a weighted genetic risk score combining 20 previously identified common genetic variants related to adult eGFRcreat with kidney outcomes in children aged 6.0 years (95% range 5.7-7.8). Childhood kidney outcomes included combined kidney volume, glomerular filtration rate (eGFR) based on creatinine levels, and microalbuminuria based on albumin and creatinine urine levels.
RESULTS
We observed that the genetic risk score based on variants related to impaired kidney function in adults was associated with a smaller combined kidney volume (P value 3.0 × 10(-3)) and with a lower eGFR (P value 4.0 × 10(-4)) in children. The genetic risk score was not associated with microalbuminuria.
CONCLUSION
Common genetic variants related to impaired kidney function in adults already lead to subclinical changes in childhood kidney outcomes. The well-known associations of kidney measures in early life with kidney disease in later life may at least be partly explained by common genetic variants.
背景
生命早期的肾脏测量指标与晚年的肾脏疾病相关。我们推测，这些关联部分可由常见基因变异来解释，这些变异会导致儿童早期肾脏体积较小且肾功能较低，以及成年期肾脏疾病。
方法
在一项基于人群的前瞻性队列研究中，我们对4119名儿童进行了检查，分析了一个加权遗传风险评分与6.0岁儿童（95%范围为5.7 - 7.8岁）肾脏结局的关联，该评分综合了20个先前确定的与成人估算肾小球滤过率（eGFRcreat）相关的常见基因变异。儿童期肾脏结局包括肾脏总体积、基于肌酐水平的肾小球滤过率（eGFR）以及基于尿白蛋白和肌酐水平的微量白蛋白尿。
结果
我们观察到，基于与成人肾功能受损相关变异的遗传风险评分与儿童较小的肾脏总体积（P值为3.0×10⁻³）和较低的eGFR（P值为4.0×10⁻⁴）相关。遗传风险评分与微量白蛋白尿无关。
结论
与成人肾功能受损相关的常见基因变异在儿童期肾脏结局中已导致亚临床变化。生命早期肾脏测量指标与晚年肾脏疾病之间的已知关联可能至少部分由常见基因变异来解释。
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