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.
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.
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Authors: Hu Li; Allison Kuipers; Candace M Kammerer; Clareanne H Bunker; Lewis H Kuller; Iva Miljkovic; Alan L Patrick; Victor W Wheeler; Joseph M Zmuda Journal: Ethn Dis Date: 2013 Impact factor: 1.847
Authors: Jeremy B Jowett; Vincent P Diego; Navaratnam Kotea; Sudhir Kowlessur; Pierrot Chitson; Thomas D Dyer; Paul Zimmet; John Blangero Journal: Twin Res Hum Genet Date: 2009-02 Impact factor: 1.587
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: W H Linda Kao; Michael J Klag; Lucy A Meoni; David Reich; Yvette Berthier-Schaad; Man Li; Josef Coresh; Nick Patterson; Arti Tandon; Neil R Powe; Nancy E Fink; John H Sadler; Matthew R Weir; Hanna E Abboud; Sharon G Adler; Jasmin Divers; Sudha K Iyengar; Barry I Freedman; Paul L Kimmel; William C Knowler; Orly F Kohn; Kristopher Kramp; David J Leehey; Susanne B Nicholas; Madeleine V Pahl; Jeffrey R Schelling; John R Sedor; Denyse Thornley-Brown; Cheryl A Winkler; Michael W Smith; Rulan S Parekh Journal: Nat Genet Date: 2008-09-14 Impact factor: 38.330
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