APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated Nephropathy
APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated Nephropathy
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DOI：
10.1681/asn.2011040388
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发表时间：
2011-11-01
影响因子：
13.6
通讯作者：
Winkler, Cheryl A.
中科院分区：
文献类型：
--
作者：
Kopp, Jeffrey B.;Nelson, George W.;Winkler, Cheryl A.
编码载脂蛋白L1的APOL 1的胰蛋白酶解变体与非裔美国人的肾脏疾病相关，但APOL 1相关的肾小球疾病是否具有独特的临床表型尚不清楚。在这里，我们确定了271例非裔美国人病例，168例欧洲裔美国人病例和939例对照受试者的APOL 1基因型。在隐性模型中，APOL 1变异体使局灶节段性肾小球硬化（FSGS）的几率高出17倍（95%CI 11至26），使HIV相关肾病（HIVAN）的几率高出29倍（95%CI 13至68）。FSGS与两个APOL 1风险等位基因相关，与较早的发病年龄（P = 0.01）和更快的进展为ESRD（P < 0.01）相关，但与其他受试者相比，对类固醇的敏感性相似。具有两个APOL 1风险等位基因的个体估计有4%的终生风险发展为FSGS，未经治疗的HIV感染者有50%的风险发展为HIVAN。携带两个APOL 1风险等位基因的影响解释了18%的FSGS和35%的HIVAN;或者，消除这种影响将使FSGS和HIVAN减少67%。一项对世界人口的调查表明，APOL 1肾脏风险等位基因仅存在于非洲染色体上。总之，携带两个APOL 1风险等位基因的非洲裔美国人患肾小球疾病的风险大大增加，APOL 1相关的FSGS发生更早，进展为ESRD更快。这些数据增加了确定APOL 1基因检测是否在临床实践中使用所需的证据基础。
Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has a distinct clinical phenotype is unknown. Here we determined APOL1 genotypes for 271 African American cases, 168 European American cases, and 939 control subjects. In a recessive model, APOL1 variants conferred seventeen-fold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-ninefold higher odds (95% CI 13 to 68) for HIV-associated nephropathy (HIVAN). FSGS associated with two APOL1 risk alleles associated with earlier age of onset (P = 0.01) and faster progression to ESRD (P < 0.01) but similar sensitivity to steroids compared with other subjects. Individuals with two APOL1 risk alleles have an estimated 4% lifetime risk for developing FSGS, and untreated HIV-infected individuals have a 50% risk for developing HIVAN. The effect of carrying two APOL1 risk alleles explains 18% of FSGS and 35% of HIVAN; alternatively, eliminating this effect would reduce FSGS and HIVAN by 67%. A survey of world populations indicated that the APOL1 kidney risk alleles are present only on African chromosomes. In summary, African Americans carrying two APOL1 risk alleles have a greatly increased risk for glomerular disease, and APOL1-associated FSGS occurs earlier and progresses to ESRD more rapidly. These data add to the evidence base required to determine whether genetic testing for APOL1 has a use in clinical practice.