Linkage of serum creatinine and glomerular filtration rate to chromosome 2 in Utah pedigrees.
BACKGROUND
Serum creatinine and creatinine clearance are used as indicators of renal function and may indicate a propensity for development of end-stage renal disease. Identifying genes related to future decreases in renal function could be important in assessing risk and defining abnormal mechanisms amenable to preventive measures. Although creatinine clearance is a better measure of renal function than serum creatinine, proper and complete urine collections in large population studies are sometimes problematic. This can lead to a loss in power to detect linkage. Therefore, in this study we also investigated serum creatinine and estimated glomerular filtration rates (GFR), both of which are more reliably measured.


METHODS
Linkage was tested in a genome scan using 49 large Utah pedigrees examined three times over 10 years to detect regions harboring genes related to reduced renal function.


RESULTS
Heritability of serum creatinine ranged from 25% to 31% across three examinations, and heritability of GFR ranged from 37% to 42%. The highest log of the odds (LOD) score for serum creatinine was found on chromosome 2 at 145 cM on the Marshfield map (D2S1334). Consistent nonparametric linkage for serum creatinine was found for all three examinations (LOD = 3.15, 2.75, and 2.00, respectively). Estimates of GFR also showed linkage to this region.


CONCLUSIONS
The consistency of linkage to chromosome 2 over longitudinally repeated measurements increases the likelihood that this region harbors a gene influencing phenotypic variation in serum creatinine and GFR. Identification of this gene could help to predict which individuals are most likely to progress to renal disease.
Hunt
Steven C
SC
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA. steve@ucvg.med.utah.edu
Coon
Hilary
H
Hasstedt
Sandra J
SJ
Cawthon
Richard M
RM
Camp
Nicola J
NJ
Wu
Lily L
LL
Hopkins
Paul N
PN
D000328:Adult; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics; D003404:Creatinine / Q000097:blood*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020521:Stroke / Q000235:genetics; D014589:Utah
D005819:Genetic Markers; D003404:Creatinine