Puppala Sobha, Arya Rector, Thameem Farook, Arar Nedal H, Bhandari Kusum, Lehman Donna M, Schneider Jennifer, Fowler Sharon, Farook Vidya S, Diego Vincent P, Almasy Laura, Blangero John, Stern Michael P, Duggirala Ravindranath, Abboud Hanna E
Southwest Foundation for Biomedical Research, Department of Genetics, P.O. Box 760549, San Antonio, TX 78254, USA.
Diabetes. 2007 Nov;56(11):2818-28. doi: 10.2337/db06-0984. Epub 2007 Aug 13.
Glomerular filtration rate (GFR) is used to assess the progression of renal disease. We performed linkage analysis to localize genes that influence GFR using estimated GFR data from the San Antonio Family Diabetes/Gallbladder Study. We also examined the effect of genotype by diabetes interaction (G x DM) on the detection of linkage to address whether genetic effects on GFR differ in diabetic and nondiabetic subjects.
GFR (N = 453) was estimated using the recently recalculated Cockcroft-Gault (GFR-CGc) and the simplified Modification of Diet in Renal Disease (GFR-4VMDRD) formulae. Both estimates of GFR exhibited significant heritabilities, but only GFR-CGc showed significant G x DM interaction. We therefore performed multipoint linkage analyses on both GFR measures using models that did not include G x DM interaction effects (Model 1) and that included G x DM interaction effects (Model 2, in the case of GFR-CGc).
The strongest evidence for linkage (Model 1) of both GFR-CGc (logarithm of odds [LOD] 2.9) and GFR-4VMDRD (LOD 2.6) occurred between markers D9S922 and D9S1120 on chromosome 9q. However, using Model 2, the strongest evidence for linkage of GFR-CGc on chromosome 2q was found near marker D2S427 (corrected LOD score [LOD(C)] 3.3) compared with the LOD score of 2.7 based on Model 1. Potential linkages (LOD or LOD(C) >or=1.2) were found only for GFR-CGc on chromosomes 3p, 3q, 4p, 8q, 11q, and 14q.
We found a major locus on chromosome 2q that differentially influences GFR in diabetic and nondiabetic environments in the Mexican-American population.
肾小球滤过率（GFR）用于评估肾脏疾病的进展。我们利用圣安东尼奥家族糖尿病/胆囊研究中的估计GFR数据进行连锁分析，以定位影响GFR的基因。我们还研究了基因型与糖尿病相互作用（G×DM）对连锁检测的影响，以探讨糖尿病和非糖尿病受试者中GFR的遗传效应是否不同。
使用最近重新计算的Cockcroft-Gault（GFR-CGc）公式和简化的肾脏疾病饮食改良（GFR-4VMDRD）公式估计GFR（N = 453）。两种GFR估计值均显示出显著的遗传力，但只有GFR-CGc显示出显著的G×DM相互作用。因此，我们使用不包括G×DM相互作用效应的模型（模型1）和包括G×DM相互作用效应的模型（对于GFR-CGc为模型2）对两种GFR测量值进行多点连锁分析。
GFR-CGc（优势对数[LOD]2.9）和GFR-4VMDRD（LOD 2.6）连锁的最强证据（模型1）出现在9号染色体9q上的标记D9S922和D9S1120之间。然而，使用模型2，与基于模型1的LOD分数2.7相比，在标记D2S427附近发现了2号染色体上GFR-CGc连锁的最强证据（校正LOD分数[LOD(C)]3.3）。仅在3号染色体p臂、3号染色体q臂、4号染色体p臂、8号染色体q臂、11号染色体q臂和14号染色体q臂上发现了GFR-CGc的潜在连锁（LOD或LOD(C)≥1.2）。
我们在2号染色体q臂上发现了一个主要位点，该位点在墨西哥裔美国人中对糖尿病和非糖尿病环境中的GFR有不同影响。
