Freedman Barry I, Langefeld Carl D, Rich Stephen S, Valis Christopher J, Sale Michèle M, Williams Adrienne H, Brown W Mark, Beck Stephanie R, Hicks Pamela J, Bowden Donald W
Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1053, USA.
J Am Soc Nephrol. 2004 Oct;15(10):2719-27. doi: 10.1097/01.ASN.0000141312.39483.4F.
Nephropathy is a complex disorder, with predisposition influenced by the interplay of both genetic and environmental factors. As part of an effort to map genes that predispose to ESRD, a genome scan was performed in 264 black pedigrees that contained 296 ESRD-affected sibling pairs using multipoint nonparametric linkage analysis methods. The cause of ESRD in index cases was consistent with hypertension-associated ESRD. Nonparametric linkage (NPL) regression provided modest evidence of linkage to 9p21.3 near D9S1121 (logarithm of odds [LOD] = 2.03), 1q25.1 near D1S1589 (LOD = 1.62), and 13q33.3 near D13S796 (LOD = 1.02). Adjusting for the evidence of linkage at the other loci through the NPL regression analysis provided evidence for linkage to 1q25.1, 6p23, and 9p21.3. The NPL regression and ordered subset analyses suggest that the evidence for linkage significantly increased with early onset of ESRD (2q32.1 LOD = 3.89, 13q13.1 LOD = 3.90), increased BMI (8p22 LOD = 3.37, 13q33.3 LOD = 5.20, 18p11.3 LOD = 2.38), early onset of hypertension (14q21.1 LOD = 3.19, 20q13.2 LOD = 2.32), and late onset of hypertension (4q13.1 LOD = 3.44, 5p15.33 LOD = 2.82). Multipoint single-locus linkage analysis provided modest evidence of linkage to nondiabetic ESRD on 9p21.3, 1q25.1 (in the region of the podocin gene), and 13q33.3. NPL regression and ordered subset analyses also identified loci on 13q13.1 and 13q33.3 as contributing to early-onset ESRD and ESRD in the presence of increased BMI, respectively. These regions should receive priority in the search for loci that contribute susceptibility to nondiabetic nephropathy.
肾病是一种复杂的病症，其易感性受到遗传和环境因素相互作用的影响。作为绘制导致终末期肾病（ESRD）易感基因图谱工作的一部分，使用多点非参数连锁分析方法，对264个黑人家系进行了基因组扫描，这些家系包含296对受ESRD影响的同胞对。索引病例中ESRD的病因与高血压相关的ESRD一致。非参数连锁（NPL）回归提供了与D9S1121附近的9p21.3（优势对数[LOD]=2.03）、D1S1589附近的1q25.1（LOD=1.62）和D13S796附近的13q33.3（LOD=1.02）连锁的适度证据。通过NPL回归分析调整其他位点的连锁证据后，提供了与1q25.1、6p23和9p21.3连锁的证据。NPL回归和有序子集分析表明，ESRD早发（2q32.1 LOD=3.89，13q13.1 LOD=3.90）、体重指数增加（8p22 LOD=3.37，13q33.3 LOD=5.20，18p11.3 LOD=2.38）、高血压早发（14q21. LOD=3.19，20q13.2 LOD=2.32）和高血压晚发（4q13.1 LOD=3.44，5p15.33 LOD=2.82）时，连锁证据显著增加。多点单基因座连锁分析提供了与9p21.3、1q25.1（在足突蛋白基因区域）和13q33.3上的非糖尿病性ESRD连锁的适度证据。NPL回归和有序子集分析还分别确定了13q13.1和13q33.3上的位点与早发性ESRD以及体重指数增加时的ESRD有关。在寻找导致非糖尿病性肾病易感性的基因座时，这些区域应作为优先考虑对象。
