A genome-wide linkage scan for genes controlling variation in urinary albumin excretion in type II diabetes.

@article{citeulike:1405478, abstract = {The main hallmark of diabetic nephropathy is elevation in urinary albumin excretion. We performed a genome-wide linkage scan in 63 extended families with multiple members with type II diabetes. Urinary albumin excretion, measured as the albumin-to-creatinine ratio (ACR), was determined in 426 diabetic and 431 nondiabetic relatives who were genotyped for 383 markers. The data were analyzed using variance components linkage analysis. Heritability (h2) of ACR was significant in diabetic (h2=0.23, P=0.0007), and nondiabetic (h2=0.39, P=0.0001) relatives. There was no significant difference in genetic variance of ACR between diabetic and nondiabetic relatives (P=0.16), and the genetic correlation (rG=0.64) for ACR between these two groups was not different from 1 (P=0.12). These results suggested that similar genes contribute to variation in ACR in diabetic and nondiabetic relatives. This hypothesis was supported further by the linkage results. Support for linkage to ACR was suggestive in diabetic relatives and became significant in all relatives for chromosome 22q (logarithm of odds, LOD=3.7) and chromosome 7q (LOD=3.1). When analyses were restricted to 59 Caucasian families, support for linkage in all relatives increased and became significant for 5q (LOD=3.4). In conclusion, genes on chromosomes 22q, 5q and 7q may contribute to variation in urinary albumin excretion in diabetic and nondiabetic individuals.}, address = {Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA. andrzej.krolewski@joslin.harvard.edu}, author = {Krolewski, A. S. and Poznik, G. D. and Placha, G. and Canani, L. and Dunn, J. and Walker, W. and Smiles, A. and Krolewski, B. and Fogarty, D. G. and Moczulski, D. and Araki, S. and Makita, Y. and Ng, D. P. and Rogus, J. and Duggirala, R. and Rich, S. S. and Warram, J. H. }, citeulike-article-id = {1405478}, doi = {10.1038/sj.ki.5000023}, issn = {0085-2538}, journal = {Kidney Int}, keywords = {dn, gwa}, month = {January}, number = {1}, pages = {129--136}, posted-at = {2007-06-23 04:29:07}, priority = {2}, title = {A genome-wide linkage scan for genes controlling variation in urinary albumin excretion in type II diabetes.}, url = {http://dx.doi.org/10.1038/sj.ki.5000023}, volume = {69}, year = {2006} }

TY - JOUR ID - citeulike:1405478 L3 - citeulike-article-id:1405478 TI - A genome-wide linkage scan for genes controlling variation in urinary albumin excretion in type II diabetes. JF - Kidney Int VL - 69 IS - 1 SP - 129 EP - 136 AD - Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA. andrzej.krolewski@joslin.harvard.edu SN - 0085-2538 N2 - The main hallmark of diabetic nephropathy is elevation in urinary albumin excretion. We performed a genome-wide linkage scan in 63 extended families with multiple members with type II diabetes. Urinary albumin excretion, measured as the albumin-to-creatinine ratio (ACR), was determined in 426 diabetic and 431 nondiabetic relatives who were genotyped for 383 markers. The data were analyzed using variance components linkage analysis. Heritability (h2) of ACR was significant in diabetic (h2=0.23, P=0.0007), and nondiabetic (h2=0.39, P=0.0001) relatives. There was no significant difference in genetic variance of ACR between diabetic and nondiabetic relatives (P=0.16), and the genetic correlation (rG=0.64) for ACR between these two groups was not different from 1 (P=0.12). These results suggested that similar genes contribute to variation in ACR in diabetic and nondiabetic relatives. This hypothesis was supported further by the linkage results. Support for linkage to ACR was suggestive in diabetic relatives and became significant in all relatives for chromosome 22q (logarithm of odds, LOD=3.7) and chromosome 7q (LOD=3.1). When analyses were restricted to 59 Caucasian families, support for linkage in all relatives increased and became significant for 5q (LOD=3.4). In conclusion, genes on chromosomes 22q, 5q and 7q may contribute to variation in urinary albumin excretion in diabetic and nondiabetic individuals. KW - dn KW - gwa AU - Krolewski, AS AU - Poznik, GD AU - Placha, G AU - Canani, L AU - Dunn, J AU - Walker, W AU - Smiles, A AU - Krolewski, B AU - Fogarty, DG AU - Moczulski, D AU - Araki, S AU - Makita, Y AU - Ng, DP AU - Rogus, J AU - Duggirala, R AU - Rich, SS AU - Warram, JH PY - 2006/01// UR - http://dx.doi.org/10.1038/sj.ki.5000023 ER -