A genome-wide search for linkage to chronic kidney disease in a community-based sample: the SAFHS.
BACKGROUND
Chronic kidney disease (CKD) phenotypes such as albuminuria measured by urinary albumin creatinine ratio (ACR), elevated serum creatinine (SrCr) and/or decreased creatinine clearance (CrCl) and glomerular filtration rate (eGFR) are major risk factors for renal and cardiovascular diseases. Epidemiological studies have reported that CKD phenotypes cluster in families suggesting a genetic predisposition. However, studies reporting chromosomal regions influencing CKD are very limited. Therefore, the purpose of this study is to identify susceptible chromosomal regions for CKD phenotypes in Mexican American families enrolled in the San Antonio Family Heart Study (SAFHS).


METHODS
We used the variance components decomposition approach (implemented in the software package SOLAR) to perform linkage analysis on 848 participants from 26 families. A total of 417 microsatellite markers were genotyped at an average interval of 10 cM spanning 22 autosomal chromosomes.


RESULTS
All phenotypes were measured by standard procedures. Mean +/- SD values of ACR, SrCr, CrCl and eGFR were 0.06 +/- 0.38, 0.85 +/- 0.72 mg/dl, 129.85 +/- 50.37 ml/min and 99.18 +/- 25.69 ml/min/1.73 m(2) body surface area, respectively. All four CKD phenotypes exhibited significant heritabilities (P < 0.0001). A genome-wide scan showed linkage on chromosome 2p25 for SrCr, CrCl and eGFR. Significant linkage was also detected on chromosome 9q21 for eGFR [logarithm of the odds (LOD) score = 3.87, P = 0.00005] and SrCr (LOD score = 2.6, P = 0.00026). ACR revealed suggestive evidence for linkage to a region on chromosome 20q12 (LOD score = 2.93, P = 0.00020).


CONCLUSIONS
Findings indicate that chromosomal regions 2p25, 9q21 and 20q12 may have functional relevance to CKD phenotypes in Mexican Americans.
Arar
Nedal H
NH
Department of Medicine/Nephrology, University of Texas Health Science Center, South Texas Veterans Health Care System, 7400 Merton Minter Blvd, San Antonio, TX 78229-4404, USA. ararn@uthscsa.edu
Voruganti
Venkata S
VS
Nath
Subrata D
SD
Thameem
Farook
F
Bauer
Richard
R
Cole
Shelley A
SA
Blangero
John
J
MacCluer
Jean W
JW
Comuzzie
Anthony G
AG
Abboud
Hanna E
HE
D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003404:Creatinine / Q000097:blood / Q000652:urine; D005260:Female; D008040:Genetic Linkage; D005828:Genetics, Population; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000503:physiopathology; D008126:Lod Score; D008297:Male; D017058:Mexican Americans; D018895:Microsatellite Repeats; D008875:Middle Aged; D012307:Risk Factors; D013781:Texas
D003404:Creatinine