Apolipoprotein L1 nephropathy risk variants associate with HDL subfraction concentration in African Americans
Apolipoprotein L1 nephropathy risk variants associate with HDL subfraction concentration in African Americans
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DOI：
10.1093/ndt/gfr542
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发表时间：
2011-11-01
影响因子：
6.1
通讯作者：
Parks, John S.
中科院分区：
文献类型：
--
作者：
Freedman, Barry I.;Langefeld, Carl D.;Parks, John S.
背景。载脂蛋白L1基因（APOL1）的编码变异与非裔美国人的非糖尿病肾病密切相关。ApoL1蛋白与循环中的高密度脂蛋白（HDL）颗粒相关。基于APOL1基因型，比较73名非洲裔美国人血浆HDL颗粒亚类浓度，以检测可能导致肾脏疾病的差异。采用核磁共振波谱法测量非糖尿病终末期肾病患者的非裔美国人一级亲属的HDL亚类浓度。参与者估计肾小球滤过率（GFRs）为80 mL/min，缺乏蛋白尿。计算了APOL1风险变异数对自然对数转换HDL亚类浓度的加性效应。参与者中58.9%为女性，平均+/- SD年龄47.2 +/- 13.3岁，GFR 92.4 +/- 18.8 mL/min。APOL1肾病风险变异为2、1和0的患者分别为36、17和20。每增加一个APOL1风险变异，平均+/- SD中等高密度脂蛋白浓度显著降低（2 vs 1 vs 0风险变异：9.0 +/- 5.6 vs 10.1 +/- 5.5 vs 13.1 +/- 8.2 μ mol/L；未经调整P = 0.0222；甘油三酯和血统调整P = 0.0162）。基于APOL1肾病风险变异数量的增加，非洲裔美国人存在较低的中等HDL亚类浓度。中等高密度脂蛋白浓度改变在apol1相关肾脏微血管疾病中的潜在机制作用应进行评估。
Background. Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with non-diabetic nephropathy in African Americans. ApoL1 proteins associate with high-density lipoprotein (HDL) particles in the circulation. Plasma HDL particle subclass concentrations were compared in 73 African Americans based on APOL1 genotypes to detect differences potentially contributing to renal disease.Methods. HDL subclass concentrations were measured using nuclear magnetic resonance spectroscopy in African American first-degree relatives of patients with non-diabetic end-stage renal disease. Participants had estimated glomerular filtration rates (GFRs) > 80 mL/min and lacked albuminuria. Additive effects of the number of APOL1 risk variants on natural logarithm-transformed HDL subclass concentrations were computed.Results. Participants were 58.9% female with mean +/- SD age 47.2 +/- 13.3 years and GFR 92.4 +/- 18.8 mL/min. The numbers with 2, 1 and 0 APOL1 nephropathy risk variants, respectively, were 36, 17 and 20. Mean +/- SD medium-sized HDL concentrations were significantly lower for each additional APOL1 risk variant (2 versus 1 versus 0 risk variants: 9.0 +/- 5.6 versus 10.1 +/- 5.5 versus 13.1 +/- 8.2 mu mol/L, respectively; P = 0.0222 unadjusted; P = 0.0162 triglyceride- and ancestry adjusted).Conclusions. Lower medium-sized HDL subclass concentrations are present in African Americans based on increasing numbers of APOL1 nephropathy risk variants. Potential mechanistic roles of altered medium HDL concentrations on APOL1-associated renal microvascular diseases should be evaluated.