NDT Advance Access published online on April 28, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn215
A genome-wide search for linkage to chronic kidney disease in a community-based sample: the SAFHS
1 Department of Medicine, University of Texas Health Science Center 2 Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio 3 South Texas Veterans Health Care System (STVHCS), TX, USA
Correspondence and offprint requests to: Nedal Arar, 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. Tel: +1-210-567-0075; Fax: +1-210-567-4712; E-mail: ararn{at}uthscsa.edu
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Abstract |
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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 m2 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).
Conclusion. Findings indicate that chromosomal regions 2p25, 9q21 and 20q12 may have functional relevance to CKD phenotypes in Mexican Americans.
Keywords: chronic kidney disease; genome-wide search; SAFHS
Received for publication: 26.11.07
Accepted in revised form: 26. 3.08