Renal Division, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
J Am Soc Nephrol. 2011 Nov;22(11):2098-105. doi: 10.1681/ASN.2011050519. Epub 2011 Oct 13.
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.
病例对照研究表明,APOL1 基因的两份拷贝均存在遗传变异的非裔美国人患高血压相关终末期肾病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验了这些风险变异,以确定在一项大型基于人群的研究中 APOL1 相关肾脏疾病的流行率,并估计 APOL1 风险变异对肾脏疾病差异的贡献。我们确定了 1825 名非裔美国人和 1042 名欧洲裔美国人的基因型。在无糖尿病的参与者中,我们发现欧洲裔美国人中有 2.3%患有微量白蛋白尿,无或仅有一个 APOL1 风险等位基因的非裔美国人中有 6.0%,有两个风险等位基因的非裔美国人中有 16.5%。此外,估计肾小球滤过率<60 ml/min/1.73 m²的参与者比例在无糖尿病的欧洲裔美国人中为 1.5%,无或仅有一个 APOL1 风险等位基因的非裔美国人中为 1.7%,有两个风险等位基因的非裔美国人中为 6.7%。APOL1 基因型与糖尿病患者的 CKD 发生率无差异相关。我们的数据表明,超过 300 万的非裔美国人可能具有高危基因型,患非糖尿病性 CKD 的风险明显增加。相比之下,没有风险基因型的非裔美国人和欧洲裔美国人似乎患非糖尿病性 CKD 的风险相似。