BACKGROUND: Albuminuria and reduced glomerular filtration rate (GFR) are markers of renal dysfunction associated with hypertension. We performed genome-wide scans to detect loci impacting these parameters in 1251 African American (AAs) and 1129 European American (EAs) hypertensive siblings from the Hypertension Genetic Epidemiology Network study. METHODS: GFR, estimated by the Modification of Diet in Renal Disease equation, and albuminuria, measured as albumin to creatinine ratio (ACR), were adjusted for gender, age, centre, mean blood pressure, anti-hypertensive medication class and diabetes status using SOLAR. Since albuminuria and abnormal GFR often coexist, we conducted bivariate linkage analyses to investigate the presence of pleiotropy. RESULTS: The phenotypic correlation between ACR and GFR was not significant in EAs (r = 0.04) and significantly negative in AAs (r = -0.17). Univariate analyses of ACR showed suggestive evidence of linkage on chromosomes 8, 16 and 17 (LOD: 2-2.8) in AAs, on chromosomes 18 and 19 (LOD = 2) in EAs, and on chromosome 19 (LOD = 2.6) when combining AAs and EAs. For GFR, suggestive linkage was found on chromosomes 7, 14 and 19 (LOD: 2.2-2.9) in AAs and on chromosomes 14, 15 and 16 (LOD: 2.1-3.3) in the combined group. Also, bivariate analyses showed a LOD score of 3.4 at 133 cM on chromosome 7 in AAs. CONCLUSIONS: Suggestive evidence for linkage to GFR and ACR was observed at many loci. The findings are consistent with previous studies. Also, indication of a pleiotropic locus was detected in chromosome 7 in AAs.
BACKGROUND:Albuminuria and reduced glomerular filtration rate (GFR) are markers of renal dysfunction associated with hypertension. We performed genome-wide scans to detect loci impacting these parameters in 1251 African American (AAs) and 1129 European American (EAs) hypertensive siblings from the Hypertension Genetic Epidemiology Network study. METHODS: GFR, estimated by the Modification of Diet in Renal Disease equation, and albuminuria, measured as albumin to creatinine ratio (ACR), were adjusted for gender, age, centre, mean blood pressure, anti-hypertensive medication class and diabetes status using SOLAR. Since albuminuria and abnormal GFR often coexist, we conducted bivariate linkage analyses to investigate the presence of pleiotropy. RESULTS: The phenotypic correlation between ACR and GFR was not significant in EAs (r = 0.04) and significantly negative in AAs (r = -0.17). Univariate analyses of ACR showed suggestive evidence of linkage on chromosomes 8, 16 and 17 (LOD: 2-2.8) in AAs, on chromosomes 18 and 19 (LOD = 2) in EAs, and on chromosome 19 (LOD = 2.6) when combining AAs and EAs. For GFR, suggestive linkage was found on chromosomes 7, 14 and 19 (LOD: 2.2-2.9) in AAs and on chromosomes 14, 15 and 16 (LOD: 2.1-3.3) in the combined group. Also, bivariate analyses showed a LOD score of 3.4 at 133 cM on chromosome 7 in AAs. CONCLUSIONS: Suggestive evidence for linkage to GFR and ACR was observed at many loci. The findings are consistent with previous studies. Also, indication of a pleiotropic locus was detected in chromosome 7 in AAs.
Authors: Nedal H Arar; Venkata S Voruganti; Subrata D Nath; Farook Thameem; Richard Bauer; Shelley A Cole; John Blangero; Jean W MacCluer; Anthony G Comuzzie; Hanna E Abboud Journal: Nephrol Dial Transplant Date: 2008-04-28 Impact factor: 5.992
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Authors: Jaclyn W Ellis; Ming-Huei Chen; Meredith C Foster; Ching-Ti Liu; Martin G Larson; Ian de Boer; Anna Köttgen; Afshin Parsa; Murielle Bochud; Carsten A Böger; Linda Kao; Caroline S Fox; Conall M O'Seaghdha Journal: Hum Mol Genet Date: 2012-04-05 Impact factor: 6.150
Authors: Cristian Pattaro; Alessandro De Grandi; Veronique Vitart; Caroline Hayward; Andre Franke; Yurii S Aulchenko; Asa Johansson; Sarah H Wild; Scott A Melville; Aaron Isaacs; Ozren Polasek; David Ellinghaus; Ivana Kolcic; Ute Nöthlings; Lina Zgaga; Tatijana Zemunik; Carsten Gnewuch; Stefan Schreiber; Susan Campbell; Nick Hastie; Mladen Boban; Thomas Meitinger; Ben A Oostra; Peter Riegler; Cosetta Minelli; Alan F Wright; Harry Campbell; Cornelia M van Duijn; Ulf Gyllensten; James F Wilson; Michael Krawczak; Igor Rudan; Peter P Pramstaller Journal: BMC Med Genet Date: 2010-03-11 Impact factor: 2.103
Authors: Nora Franceschini; Kari E North; Donna Arnett; James S Pankow; Jay H Chung; Lisa Baird; Mark F Leppert; John H Eckfeldt; Eric Boerwinkle; C Charles Gu; Cora E Lewis; Richard H Myers; Stephen T Turner; Alan Weder; W H Linda Kao; Thomas H Mosley; Aravinda Chakravarti; Holly Kramer; Jinghui Zhang; Steven C Hunt Journal: Am J Hypertens Date: 2009-03-05 Impact factor: 2.689
Authors: Amy K Mottl; Suma Vupputuri; Shelley A Cole; Laura Almasy; Harald H H Göring; Vincent P Diego; Sandra Laston; Nawar Shara; Elisa T Lee; Lyle G Best; Richard R Fabsitz; Jean W MacCluer; Jason G Umans; Kari E North Journal: J Am Soc Nephrol Date: 2009-04-15 Impact factor: 10.121