Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
J Am Soc Nephrol. 2013 Sep;24(9):1484-91. doi: 10.1681/ASN.2013010113. Epub 2013 Jun 13.
Although case-control studies suggest that African Americans with common coding variants in the APOL1 gene are 5-29 times more likely than those individuals without such variants to have focal segmental glomerulosclerosis, HIV-associated nephropathy, or ESRD, prospective studies have not yet evaluated the impact of these variants on CKD in a community-based sample of African Americans. Here, we studied whether the APOL1 G1 and G2 risk alleles associate with the development of CKD and progression to ESRD by analyzing data from 3067 African Americans in the Atherosclerosis Risk in Communities Study who did not have CKD at baseline. Carrying two risk alleles associated with a 1.49-fold increased risk of CKD (95% CI=1.02 to 2.17) and a 1.88-fold increased risk of ESRD (95% CI=1.20 to 2.93) compared with zero or one risk allele; associations persisted after adjusting for European ancestry. Among participants who developed CKD, those participants with two risk alleles were more likely to progress to ESRD than their counterparts with zero or one risk allele (HR=2.22, 95% CI=1.01 to 4.84). In conclusion, APOL1 risk variants are risk factors for the development of CKD and progression from CKD to ESRD among African Americans in the general population.
虽然病例对照研究表明，携带 APOL1 基因常见编码变异的非裔美国人患局灶节段性肾小球硬化症、HIV 相关肾病或终末期肾病的风险比没有此类变异的个体高 5-29 倍，但前瞻性研究尚未评估这些变异在非裔美国人社区样本中对 CKD 的影响。在这里，我们通过分析未患有 CKD 的 3067 名非裔美国人的社区动脉粥样硬化风险研究（Atherosclerosis Risk in Communities Study）数据，研究了 APOL1 G1 和 G2 风险等位基因是否与 CKD 的发生和 ESRD 的进展相关。与零或一个风险等位基因相比，携带两个风险等位基因与 CKD 的风险增加 1.49 倍（95%CI=1.02 至 2.17）和 ESRD 的风险增加 1.88 倍（95%CI=1.20 至 2.93）相关；在调整欧洲血统后，关联仍然存在。在发生 CKD 的参与者中，与携带零或一个风险等位基因的参与者相比，携带两个风险等位基因的参与者更有可能进展为 ESRD（HR=2.22，95%CI=1.01 至 4.84）。总之，APOL1 风险变异是非裔美国人中普通人群 CKD 发生和从 CKD 进展到 ESRD 的危险因素。
