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Diabetes Publish Ahead of Print published online ahead of print September 27, 2007
DOI: 10.2337/db06-0984
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Original Research

Genotype by Diabetes Interaction Effects on the Detection of Linkage of Glomerular Filtration Rate (GFR) to a Region on Chromosome 2q in Mexican Americans

Sobha Puppala, Ph.D1, Rector Arya, Ph.D2, Farook Thameem, Ph.D3, Nedal H. Arar, Ph.D3, Kusum Bhandari, M.D2, Donna M. Lehman, Ph.D2, Jennifer Schneider, B.A1, Sharon Fowler, M.P.H2, Vidya S. Farook, Ph.D1, Vincent P. Diego, Ph.D1, Laura Almasy, Ph.D1, John Blangero, Ph.D1, Michael P. Stern, M.D2, Ravindranath Duggirala, Ph.D1, and Hanna E. Abboud, M.D3

1Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX
2 Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX
3 Division of Nephrology, Department of Medicine, University of Texas Health Science Center, San Antonio, TX

Objective: Glomerular filtration rate (GFR) is used to assess the progression of renal disease. We performed linkage analysis to localize genes that influence GFR, using estimated GFR data from the San Antonio Family Diabetes/Gallbladder Study. We also examined the effect of genotype by diabetes interaction (G x DM) on the detection of linkage to address whether genetic effects on GFR differ in diabetics and non-diabetics.

Research Design and Methods: GFR (N = 453) was estimated using the recently recalculated Cockcroft-Gault (GFR-CGc) and the simplified Modification of Diet in Renal Disease (GFR-4VMDRDc) formulae. Both estimates of GFR exhibited significant heritabilities, but only GFR-CGc showed significant G x DM interaction. We therefore performed multipoint linkage analyses on both GFR measures using models that did not include G x DM interaction effects (Model 1), and that included G x DM interaction effects (Model 2, in the case of GFR-CGc).

Results: The strongest evidence for linkage (Model 1) of both GFR-CGc (LOD = 2.9) and GFR-4VMDRD (LOD = 2.6) occurred between markers D9S922 and D9S1120 on chromosome 9q. However, using Model 2, the strongest evidence for linkage of GFR-CGc on chromosome 2q was found near marker D2S427 (LODC = 3.3) compared to the LOD score of 2.7 based on Model 1. Potential linkages (LOD or LODC ≥1.2) were found only for GFR-CGc on chromosomes 3p, 3q, 4p, 8q, 11q and 14q.

Conclusion: We found a major locus on chromosome 2q that differentially influences GFR in diabetic and non-diabetic environments in the Mexican American population.

Key Words: Renal function • linkage • variance components • genotype by diabetes interaction


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Copyright © 2007 by the American Diabetes Association.