Population-Based Risk Assessment of APOL1 on Renal Disease
Population-Based Risk Assessment of APOL1 on Renal Disease
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DOI：
10.1681/asn.2011050519
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发表时间：
2011-11-01
影响因子：
13.6
通讯作者：
Pollak, Martin R.
中科院分区：
文献类型：
--
作者：
Friedman, David J.;Kozlitina, Julia;Pollak, Martin R.
病例对照研究表明，在APOL 1基因的两个拷贝中都有遗传变异的非裔美国人患高血压所致ESRD和局灶节段性肾小球硬化症的风险增加。在此，我们在达拉斯心脏研究中检测了这些风险变异，以确定APOL 1相关肾脏疾病在一项大规模人群研究中的患病率，并估计APOL 1风险变异对肾脏疾病差异的贡献。我们确定了1825名非洲裔美国人和1042名欧洲裔美国人的基因型。在没有糖尿病的参与者中，我们发现2.3%的欧洲裔美国人，6.0%的非洲裔美国人没有或有一个APOL 1风险等位基因，16.5%的非洲裔美国人有两个风险等位基因。此外，估计GFR < 60 ml/min/1.73 m2的受试者比例在非糖尿病的欧洲裔美国人中为1.5%，在没有或有一个APOL 1风险等位基因的非洲裔美国人中为1.7%，在有两个风险等位基因的非洲裔美国人中为6.7%。APOL 1基因型与糖尿病研究参与者的CKD发生率无任何差异。我们的数据表明，超过300万非洲裔美国人可能有高风险基因型，并在非糖尿病CKD的风险显着增加。相比之下，非裔美国人没有风险基因型和欧洲美国人似乎有类似的风险发展为非糖尿病CKD。
Case-control studies suggest that African Americans with genetic variants in both copies of APOL1 have increased risk for hypertension-attributable ESRD and focal segmental glomerulosclerosis. Here, we tested these risk variants in the Dallas Heart Study to ascertain the prevalence of APOL1-associated renal disease in a large population-based study and to estimate the contribution of APOL1 risk variants to disparities in renal disease. We determined the genotype of 1825 African Americans and 1042 European Americans. Among participants without diabetes, we identified microalbuminuria in 2.3% of European Americans, 6.0% of African Americans with no or one APOL1 risk allele, and 16.5% of African Americans with two risk alleles. In addition, the proportions of participants with estimated GFR < 60 ml/min per 1.73 m(2) was 1.5% for nondiabetic European Americans, 1.7% for African Americans with no or one APOL1 risk allele, and 6.7% for African Americans with two risk alleles. The APOL1 genotype did not associate with any differences in rates of CKD for study participants with diabetes. Our data suggest that more than 3 million African Americans likely have the high-risk genotype and are at markedly increased risk for nondiabetic CKD. In contrast, African Americans without the risk genotype and European Americans appear to have similar risk for developing nondiabetic CKD.