基因变异体与非裔美国人的肾脏疾病有关联: 研究人员报告说，那些携带某一基因变异体的非裔美国人罹患肾脏疾病的风险会增加。 Giulio Genovese及其同僚发现， 那些在APOL1基因（这是在第22条染色体上的一个编码载脂蛋白L-1的基因）中携带特别基因序列变异体的非洲裔美国人，其发生可导致高血压的终末期肾病及局灶节段性肾小球硬化（该病与疤痕组织在肾脏某些部分的积累有关）的风险会增加。 文章的作者报告说，这些发生肾病的危险等位基因出现在超过30%的非洲裔美国人的染色体中。这些作者说，研究这些等位基因是如何促成肾脏损害的对了解及有可能防止具有近代非洲祖先的个人的肾病发生是非常重要的。
APOL1 的功能之一是削弱锥虫这种寄生虫并将其杀灭。 有趣的是，来自该危险等位基因的APOL1（但不是来自由欧洲人及其他种族的该等位基因的APOL1）可杀灭引起非洲人昏睡病的锥虫Trypanosoma brucei rhodesiense（布氏锥虫罗得西亚亚种）。 容有这些危险等位基因的染色体区域还显示了正向选择的迹象，这意味着这些基因在某一时刻在人群中曾快速地扩散。 文章的作者猜测，在非洲人中的一种关键性的存活因子的演化可能促成了在非洲裔美国人中的肾病高发生率。这一诱人的想法仍然需要接受严格的检验。
Article #24: "Association of Trypanolytic ApoL1 Variants with Kidney Disease in African-Americans," by G. Genovese; D.J. Friedman; A.J. Bernhardy; M.R. Pollak at Beth Israel Deaconess Medical Center in Boston, MA; G. Genovese; D.J. Friedman; A.J. Bernhardy; M.R. Pollak at Harvard Medical School in Boston, MA; G. Genovese at Dartmouth College in Hanover, NH; M.D. Ross; A.U. Knob at Brigham and Women’s Hospital in Boston, MA; L. Lecordier; P. Uzureau; B. Vanhollebeke; E. Pays at Université Libre de Bruxelles in Gosselies, Belgium; B.I. Freedman; D.W. Bowden; C.D. Langefeld; P.J. Hicks at Wake Forest University School of Medicine in Winston-Salem, NC; K. Oleksyk at University of Puerto Rico at Mayaguez in Mayaguez, PR; C.A. Winkler at SAIC-Frederick, Inc in Frederick, MD; C.A. Winkler at National Cancer Institute--Frederick in Frederick, MD; G.W. Nelson; J.B. Kopp at National Institute of Diabetes, Digestive, and Kidney Disease, National Institutes of Health in Bethesda, MD; M.R. Pollak at Broad Institute of Harvard and MIT in Cambridge, MA.
联系人: Martin R. Pollak，mpollak@bidmc.harvard.edu (电子邮件)。Etienne Pays，epays@ulb.ac.be (电子邮件)。
Published Online July 15, 2010
Science DOI: 10.1126/science.1193032
Reports
Association of Trypanolytic ApoL1 Variants with Kidney Disease in African-Americans
African-Americans have higher rates of kidney disease than European-Americans. Here, we show that in African-Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. Apolipoprotein L-1 (ApoL1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African-Americans.
