世界贸易中心救援人员肾小球滤过率下降的多基因关联。
Polygenic association of glomerular filtration rate decline in world trade center responders.
机构信息
Division of Nephrology, Department of Medicine, Stony Brook University, 100 Nicolls Road, HSCT16-080E, Stony Brook, NY, USA.
Department of Family, Population, and Preventative Medicine, Stony Brook University, Stony Brook, NY, USA.
出版信息
BMC Nephrol. 2022 Oct 28;23(1):347. doi: 10.1186/s12882-022-02967-5.
BACKGROUND
The factors associated with estimated glomerular filtrate rate (eGFR) decline in low risk adults remain relatively unknown. We hypothesized that a polygenic risk score (PRS) will be associated with eGFR decline.
METHODS
We analyzed genetic data from 1,601 adult participants with European ancestry in the World Trade Center Health Program (baseline age 49.68 ± 8.79 years, 93% male, 23% hypertensive, 7% diabetic and 1% with cardiovascular disease) with ≥ three serial measures of serum creatinine. PRSs were calculated from an aggregation of single nucleotide polymorphisms (SNPs) from a recent, large-scale genome-wide association study (GWAS) of rapid eGFR decline. Generalized linear models were used to evaluate the association of PRS with renal outcomes: baseline eGFR and CKD stage, rate of change in eGFR, stable versus declining eGFR over a 3-5-year observation period. eGFR decline was defined in separate analyses as "clinical" (> -1.0 ml/min/1.73 m/year) or "empirical" (lower most quartile of eGFR slopes).
RESULTS
The mean baseline eGFR was ~ 86 ml/min/1.73 m. Subjects with decline in eGFR were more likely to be diabetic. PRS was significantly associated with lower baseline eGFR (B = -0.96, p = 0.002), higher CKD stage (OR = 1.17, p = 0.010), decline in eGFR (OR = 1.14, p = 0.036) relative to stable eGFR, and the lower quartile of eGFR slopes (OR = 1.21, p = 0.008), after adjusting for established risk factors for CKD.
CONCLUSION
Common genetic variants are associated with eGFR decline in middle-aged adults with relatively low comorbidity burdens.
背景
低风险成年人中与估算肾小球滤过率（eGFR）下降相关的因素尚不清楚。我们假设多基因风险评分（PRS）与 eGFR 下降有关。
方法
我们分析了来自 World Trade Center 健康计划的 1601 名具有欧洲血统的成年参与者的遗传数据（基线年龄为 49.68±8.79 岁，93%为男性，23%为高血压，7%为糖尿病，1%为心血管疾病），这些参与者至少有三次血清肌酐的连续测量值。PRS 是根据最近一项大规模全基因组关联研究（GWAS）中对 eGFR 快速下降的单核苷酸多态性（SNP）的聚集计算得出的。使用广义线性模型评估 PRS 与肾脏结局的关联：基线 eGFR 和 CKD 分期、eGFR 变化率、在 3-5 年观察期内 eGFR 稳定或下降。在单独的分析中，eGFR 下降被定义为“临床”（> -1.0 ml/min/1.73 m/year）或“经验”（eGFR 斜率最低四分位数）。
结果
平均基线 eGFR 约为 86 ml/min/1.73 m。eGFR 下降的受试者更有可能患有糖尿病。PRS 与较低的基线 eGFR（B = -0.96，p = 0.002）、较高的 CKD 分期（OR = 1.17，p = 0.010）、eGFR 下降（OR = 1.14，p = 0.036）相关，而与 eGFR 稳定相关，并且 eGFR 斜率的较低四分位数（OR = 1.21，p = 0.008），在调整了 CKD 的既定危险因素后。
结论
在患有相对低合并症负担的中年成年人中，常见的遗传变异与 eGFR 下降有关。
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