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

A. S. Krolewski, G. D. Poznik, G. Placha, L. Canani, J. Dunn, W. Walker, A. Smiles, B. Krolewski, D. G. Fogarty, D. Moczulski, S. Araki, Y. Makita, D. P.K. Ng, J. Rogus, R. Duggirala, S. S. Rich, J. H. Warram

Research output: Contribution to journalArticle

92 Scopus citations

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 (h 2) of ACR was significant in diabetic (h 2 = 0.23, P = 0.0007), and nondiabetic (h 2 = 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 (r G = 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.

Original languageEnglish (US)
Pages (from-to)129-136
Number of pages8
JournalKidney international
Volume69
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Keywords

  • Genetics of diabetic nephropathy
  • QTL for urinary albumin excretion
  • QTLs on chromosomes 5q, 7q and 22q
  • Variance components linkage analysis

ASJC Scopus subject areas

  • Nephrology

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    Krolewski, A. S., Poznik, G. D., Placha, G., Canani, L., Dunn, J., Walker, W., Smiles, A., Krolewski, B., Fogarty, D. G., Moczulski, D., Araki, S., Makita, Y., Ng, D. P. K., Rogus, J., Duggirala, R., Rich, S. S., & Warram, J. H. (2006). A genome-wide linkage scan for genes controlling variation in urinary albumin excretion in type II diabetes. Kidney international, 69(1), 129-136. https://doi.org/10.1038/sj.ki.5000023