Kopp Jeffrey B, Winkler Cheryl
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.
Kidney Int Suppl. 2003 Feb(83):S43-9. doi: 10.1046/j.1523-1755.63.s83.10.x.
Human immunodeficiency virus-1 (HIV-1) infection is associated with several glomerular syndromes, the most prevalent of which is HIV-associated focal segmental glomerulosclerosis (FSGS). At present, HIV-associated FSGS may account for up to 30% of patients in the United States entering end-stage renal disease (ESRD) as a consequence of FSGS. The mechanisms responsible for HIV-associated FSGS are not well defined, but evidence has been presented in favor of direct infection of renal parenchymal cells and toxicity of HIV-1 accessory proteins. HIV-associated FSGS has a striking predilection for patients of African descent. This likely has a genetic basis, although the gene or genes responsible have not yet been identified. One approach is to examine candidate genes for polymorphisms that are associated with disease. Another approach uses a genome-wide scan, relying upon linkage disequilibrium between DNA markers and the disease gene, to identify the causal gene or genes. African Americans are an admixed population, with genetic contributions from African, European, and Native American populations. In admixed populations, linkage disequilibrium between disease genes and marker genes can be exploited to identify disease genes, using an approach termed mapping by admixture linkage disequilibrium (MALD).
人类免疫缺陷病毒1型（HIV-1）感染与多种肾小球综合征相关，其中最常见的是HIV相关性局灶节段性肾小球硬化（FSGS）。目前，在美国，因FSGS进入终末期肾病（ESRD）的患者中，HIV相关性FSGS患者可能占多达30%。导致HIV相关性FSGS的机制尚未完全明确，但已有证据支持肾实质细胞的直接感染以及HIV-1辅助蛋白的毒性作用。HIV相关性FSGS对非洲裔患者有显著的偏好。这可能有遗传基础，尽管相关基因尚未确定。一种方法是检测与疾病相关的候选基因的多态性。另一种方法是进行全基因组扫描，依靠DNA标记与疾病基因之间的连锁不平衡来确定致病基因。非裔美国人是一个混合群体，有来自非洲、欧洲和美洲原住民群体的基因贡献。在混合群体中，可以利用疾病基因与标记基因之间的连锁不平衡，采用一种称为混合连锁不平衡定位（MALD）的方法来识别疾病基因。
