Freedman Barry I, Bowden Donald W, Rich Stephen S, Valis Christopher J, Sale Michèle M, Hicks Pamela J, Langefeld Carl D
Department of Internal Medicine/Section on Nephrology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1053, USA.
Nephrol Dial Transplant. 2005 Apr;20(4):712-8. doi: 10.1093/ndt/gfh704. Epub 2005 Feb 8.
In an attempt to map the genes predisposing to the common, complex aetiologies of end-stage renal disease (ESRD), we performed a genome-wide scan in 1023 individuals with chronic kidney disease (946 dialysis dependent and 77 with advanced chronic renal failure) from 483 African American families.
The study sample comprised 563 ESRD-affected sibling pairs, with nephropathy attributed to diabetes mellitus, chronic glomerular disease or hypertension. Multipoint non-parametric linkage (NPL) analysis methods were employed.
NPL regression provided modest evidence of linkage to 13q33.3 near D13S796 [log of the odds (LOD) = 1.72], 9q34.3 near D9S1826 (LOD = 1.22), 4p15.32 near D4S2639 (LOD = 1.11) and 1q25.1 near D1S1589 (LOD = 1.01). Adjusting for the evidence of linkage at the other loci using NPL regression analysis provided evidence for linkage to 4p15.32, 9q34.3 and 13q33.3. NPL regression interaction and ordered subset analysis (OSA) suggested that the evidence for linkage to ESRD significantly increased with higher body mass index (BMI) at 13q33.3 (LOD = 4.94 in 61% of families with the highest BMI). Additionally, OSA suggested that linkage significantly improved in the 13% of families with earliest age at ESRD onset (LOD = 3.05 at 2q32.1) and in the 16% of families with latest age at ESRD onset (LOD = 2.47 at 10q26.3).
Multipoint single-locus linkage analysis provided modest evidence of linkage to all-cause ESRD in African Americans on 13q33.3, and NPL regression and OSA suggested that evidence for linkage in this region markedly increased in obese families. This region, as well as 9q34.3, 4p15.32 and 1q25.1, should receive priority in the search for loci contributing to ESRD susceptibility in African Americans.
为了绘制导致终末期肾病（ESRD）常见复杂病因的易感基因图谱，我们对来自483个非裔美国家庭的1023例慢性肾病患者（946例依赖透析，77例患有晚期慢性肾衰竭）进行了全基因组扫描。
研究样本包括563对受ESRD影响的同胞对，其肾病归因于糖尿病、慢性肾小球疾病或高血压。采用多点非参数连锁（NPL）分析方法。
NPL回归提供了与13q33.3靠近D13S796处连锁的适度证据[优势对数（LOD）=1.72]，9q34.3靠近D9S1826处（LOD = 1.22），4p15.32靠近D4S2639处（LOD = 1.11）以及1q25.1靠近D1S1589处（LOD = 1.01）。使用NPL回归分析对其他位点的连锁证据进行校正后，提供了与4p15.32、9q34.3和13q33.3连锁的证据。NPL回归相互作用和有序子集分析（OSA）表明，在13q33.3处，与ESRD连锁的证据随着体重指数（BMI）升高而显著增加（在BMI最高的61%的家庭中LOD = 4.94）。此外，OSA表明，在ESRD发病年龄最早的13%的家庭中连锁显著改善（在2q32.1处LOD = 3.05），在ESRD发病年龄最晚的16%的家庭中连锁也显著改善（在10q26.3处LOD = 2.47）。
多点单基因座连锁分析为非裔美国人中全因ESRD与13q33.3连锁提供了适度证据，NPL回归和OSA表明该区域在肥胖家庭中的连锁证据显著增加。该区域以及9q34.3、4p15.32和1q25.1在寻找导致非裔美国人ESRD易感性的基因座时应优先考虑。
