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

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 diabet...

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Published in:	Kidney international Vol. 69; no. 1; pp. 129 - 136
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Inc 01-01-2006 Nature Publishing Elsevier Limited
Subjects:	Adult Aged Albuminuria - genetics Biological and medical sciences Creatinine - urine Diabetes Mellitus, Type 2 - genetics Diabetes. Impaired glucose tolerance Diabetic Nephropathies - genetics Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Female Genetic Linkage genetics of diabetic nephropathy Humans Lod Score Male Medical sciences Middle Aged Nephrology. Urinary tract diseases QTL for urinary albumin excretion QTLs on chromosomes 5q, 7q and 22q Quantitative Trait Loci Urinary system involvement in other diseases. Miscellaneous Urinary tract. Prostate gland variance components linkage analysis variance components linkage analysis QTL for urinary albumin excretion genetics of diabetic nephropathy QTLs on chromosomes 5q, 7q and 22q Endocrinopathy Kidney disease Genetic mapping Type 2 diabetes Urine 7q and 22q Excretion Nephrology Urinary system disease Quantitative character Albumin Variations Metabolic diseases Chromosome G22 Chromosome B5 Chromosome C7 Urology Gene Genetic linkage Genetics Diabetic nephropathy Variance component Proteinuria genetics of diabetic nephropathy; QTL for urinary albumin excretion; variance components linkage analysis; QTLs on chromosomes 5q
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0085-2538 1523-1755
DOI:	10.1038/sj.ki.5000023