A genome-wide linkage scan for genes controlling variation in renal function estimated by serum cystatin C levels in extended families with type 2 diabetes.
We performed a variance components linkage analysis of renal function, measured as glomerular filtration rate (GFR), in 63 extended families with multiple members with type 2 diabetes. GFR was estimated from serum concentrations of cystatin C and creatinine in 406 diabetic and 428 nondiabetic relatives. Results for cystatin C were summarized because they are superior to creatinine results. GFR aggregates in families with significant heritability (h(2)) in diabetic (h(2) = 0.45, P < 1 x 10(-5)) and nondiabetic (h(2) = 0.36, P < 1 x 10(-3)) relatives. Genetic correlation (r(G) = 0.35) between the GFR of diabetic and nondiabetic relatives was less than one (P = 0.01), suggesting that genes controlling GFR variation in these groups are different. Linkage results supported this interpretation. In diabetic relatives, linkage was strong on chromosome 2q (logarithm of odds [LOD] = 4.1) and suggestive on 10q (LOD = 3.1) and 18p (LOD = 2.2). In nondiabetic relatives, linkage was suggestive on 3q (LOD = 2.2) and 11p (LOD = 2.1). When diabetic and nondiabetic relatives were combined, strong evidence for linkage was found only on 7p (LOD = 4.0). In conclusion, partially distinct sets of genes control GFR variation in relatives with and without diabetes on chromosome 2q, possibly on 10q and 18p in the former, and on 7p in both. None of these genes overlaps with genes controlling variation in urinary albumin excretion.
Placha
Grzegorz
G
Section on Genetics and Epidemiology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215, USA.
Poznik
G David
GD
Dunn
Jonathon
J
Smiles
Adam
A
Krolewski
Bozena
B
Glew
Timothy
T
Puppala
Sobha
S
Schneider
Jennifer
J
Rogus
John J
JJ
Rich
Stephen S
SS
Duggirala
Ravindranath
R
Warram
James H
JH
Krolewski
Andrzej S
AS
D000328:Adult; D017668:Age of Onset; D000368:Aged; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D002887:Chromosomes, Human, Pair 18; D002889:Chromosomes, Human, Pair 2; D002897:Chromosomes, Human, Pair 7; D055316:Cystatin C; D015891:Cystatins / Q000097:blood* / Q000235:genetics*; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D005190:Family; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests; D008875:Middle Aged; D012016:Reference Values
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D004247:DNA