Diabetes, Vol 49, Issue 6 1057-1063, Copyright © 2000 by American Diabetes Association

ARTICLES

Segregation analysis of urinary albumin excretion in families with type 2 diabetes

DG Fogarty, LS Hanna, M Wantman, JH Warram, AS Krolewski and SS Rich
Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA.

Elevated urinary albumin excretion (UAE) is a predictor of the development of nephropathy and cardiovascular mortality. To study whether genetic factors may determine UAE, we examined familial aggregation of UAE in 96 large multigenerational pedigrees ascertained for type 2 diabetes. A total of 1,269 subjects had UAE measured as the urinary albumin-to-creatinine ratio (ACR). This included 630 subjects with type 2 diabetes and 639 subjects without diabetes. A significant correlation (Spearman's correlation 0.34, P < 0.001) was found between the median ACR values determined separately in nondiabetic and diabetic members of the same family. To determine whether this familial aggregation of ACR could be explained by the transmission of 1 or more major genes and thus be suitable for gene mapping studies, segregation analyses were performed. In these analyses, ACR was modeled as a continuous trait with the inclusion of age, sex, and duration of diabetes as covariates. Likelihood ratio tests were performed to test competing hypotheses, and Akaike's information criterion was used to determine the most parsimonious models. The Mendelian model with multifactorial inheritance was supported more strongly than Mendelian inheritance alone. These analyses suggested that the best model for ACR levels was multifactorial with evidence for a common major gene. When the analyses were repeated for diabetic subjects only, the evidence for Mendelian inheritance was improved, although a single major locus with additional multifactorial effects was more strongly supported. The results from the current study suggest that levels of UAE are determined by a mixture of genes with large and small effects as well as other measured covariates, such as diabetes.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. I. Freedman, M. Bostrom, P. Daeihagh, and D. W. Bowden Genetic Factors in Diabetic Nephropathy Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1306 - 1316. [Abstract] [Full Text] [PDF]

				A. Schulz, J. Weiss, M. Schlesener, J. Hansch, M. Wehland, N. Wendt, P. Kossmehl, A. Sietmann, D. Grimm, M. Stoll, et al. Development of Overt Proteinuria in the Munich Wistar Fromter Rat Is Suppressed by Replacement of Chromosome 6 in a Consomic Rat Strain J. Am. Soc. Nephrol., January 1, 2007; 18(1): 113 - 121. [Abstract] [Full Text] [PDF]

				J. R. Sedor Frontiers in Diabetic Nephropathy: Can We Predict Who Will Get Sick? J. Am. Soc. Nephrol., February 1, 2006; 17(2): 336 - 338. [Full Text] [PDF]

				K. G. Ewens, R. A. George, K. Sharma, F. N. Ziyadeh, and R. S. Spielman Assessment of 115 Candidate Genes for Diabetic Nephropathy by Transmission/Disequilibrium Test Diabetes, November 1, 2005; 54(11): 3305 - 3318. [Abstract] [Full Text] [PDF]

				A.-K. Siegel, P. Kossmehl, M. Planert, A. Schulz, M. Wehland, M. Stoll, J. A. Bruijn, E. de Heer, and R. Kreutz Genetic linkage of albuminuria and renal injury in Dahl salt-sensitive rats on a high-salt diet: comparison with spontaneously hypertensive rats Physiol Genomics, July 8, 2004; 18(2): 218 - 225. [Abstract] [Full Text] [PDF]

				S.-J. Pinto-Sietsma, S.-M. Herrmann, K. Schmidt-Petersen, T. Niu, H. L. Hillege, W. M.T. Janssen, D. de Zeeuw, P. de Jong, and R. Kreutz Role of the Endothelin-1 Gene Locus for Renal Impairment in the General Nondiabetic Population J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2596 - 2602. [Abstract] [Full Text] [PDF]

				B. I. Freedman, S. R. Beck, S. S. Rich, G. Heiss, C. E. Lewis, S. Turner, M. A. Province, K. L. Schwander, D. K. Arnett, and B. G. Mellen A Genome-Wide Scan for Urinary Albumin Excretion in Hypertensive Families Hypertension, September 1, 2003; 42(3): 291 - 296. [Abstract] [Full Text] [PDF]

				A. Poyan Mehr, A.-K. Siegel, P. Kossmehl, A. Schulz, R. Plehm, J. A. de Bruijn, E. de Heer, and R. Kreutz Early onset albuminuria in Dahl rats is a polygenetic trait that is independent from salt loading Physiol Genomics, August 15, 2003; 14(3): 209 - 216. [Abstract] [Full Text] [PDF]

				S. K. Iyengar, K. A. Fox, M. Schachere, F. Manzoor, M. E. Slaughter, A. M. Covic, S. M. Orloff, P. S. Hayden, J. M. Olson, J. R. Schelling, et al. Linkage Analysis of Candidate Loci for End-Stage Renal Disease due to Diabetic Nephropathy J. Am. Soc. Nephrol., July 1, 2003; 14(90002): S195 - 201. [Abstract] [Full Text] [PDF]

				A. Schulz, A. Litfin, P. Kossmehl, and R. Kreutz Genetic Dissection of Increased Urinary Albumin Excretion in the Munich Wistar Fromter Rat J. Am. Soc. Nephrol., November 1, 2002; 13(11): 2706 - 2714. [Abstract] [Full Text] [PDF]

				J. B. Meigs, R. B. D'Agostino Sr., D. M. Nathan, N. Rifai, and P. W.F. Wilson Longitudinal Association of Glycemia and Microalbuminuria: The Framingham Offspring Study Diabetes Care, June 1, 2002; 25(6): 977 - 983. [Abstract] [Full Text] [PDF]

				J. J. Rogus, J. H. Warram, and A. S. Krolewski Genetic Studies of Late Diabetic Complications: The Overlooked Importance of Diabetes Duration Before Complication Onset Diabetes, June 1, 2002; 51(6): 1655 - 1662. [Abstract] [Full Text] [PDF]

				L. J. Scott, J. H. Warram, L. S. Hanna, L. M. B. Laffel, L. Ryan, and A. S. Krolewski A Nonlinear Effect of Hyperglycemia and Current Cigarette Smoking Are Major Determinants of the Onset of Microalbuminuria in Type 1 Diabetes Diabetes, December 1, 2001; 50(12): 2842 - 2849. [Abstract] [Full Text] [PDF]