BACKGROUND: Recent experimental evidence suggests that DNA damage and cell cycle regulatory proteins are involved in kidney injury and apoptosis. The checkpoint 2 gene (CHEK2) is an important transducer in DNA damage signaling pathways in response to injury, and therefore, CHEK2 variants may affect susceptibility to kidney disease. METHODS: We used tag-single-nucleotide polymorphisms (tag-SNPs) to evaluate the association of the CHEK2 with kidney function (estimated glomerular filtration rate, eGFR) in 1,549 African-American and 1,423 white Hypertension Genetic Epidemiology Network (HyperGEN) participants. We performed replication analyses in the Genetic Epidemiology Network of Arteriopathy (GENOA) participants (1,746 African Americans and 1,418 whites), GenNet participants (706 whites), and Atherosclerosis Risk in Communities (ARIC) study participants (3,783 African Americans and 10,936 whites). All analyses were race-stratified and used additive genetic models with adjustments for covariates and for family structure, if needed. RESULTS: One tag-SNP, rs5762764, was associated with eGFR in HyperGEN (P = 0.003) and GENOA white participants (P = 0.009), and it was significantly associated with eGFR in meta-analyses (P = 0.002). The associations were independent of type 2 diabetes. CONCLUSIONS: These results suggest that CHEK2 variants may influence eGFR in the context of hypertension.
BACKGROUND: Recent experimental evidence suggests that DNA damage and cell cycle regulatory proteins are involved in kidney injury and apoptosis. The checkpoint 2 gene (CHEK2) is an important transducer in DNA damage signaling pathways in response to injury, and therefore, CHEK2 variants may affect susceptibility to kidney disease. METHODS: We used tag-single-nucleotide polymorphisms (tag-SNPs) to evaluate the association of the CHEK2 with kidney function (estimated glomerular filtration rate, eGFR) in 1,549 African-American and 1,423 white Hypertension Genetic Epidemiology Network (HyperGEN) participants. We performed replication analyses in the Genetic Epidemiology Network of Arteriopathy (GENOA) participants (1,746 African Americans and 1,418 whites), GenNet participants (706 whites), and Atherosclerosis Risk in Communities (ARIC) study participants (3,783 African Americans and 10,936 whites). All analyses were race-stratified and used additive genetic models with adjustments for covariates and for family structure, if needed. RESULTS: One tag-SNP, rs5762764, was associated with eGFR in HyperGEN (P = 0.003) and GENOA white participants (P = 0.009), and it was significantly associated with eGFR in meta-analyses (P = 0.002). The associations were independent of type 2 diabetes. CONCLUSIONS: These results suggest that CHEK2 variants may influence eGFR in the context of hypertension.
Authors: Allan J Collins; Bertram Kasiske; Charles Herzog; Blanche Chavers; Robert Foley; David Gilbertson; Richard Grimm; Jiannong Liu; Thomas Louis; Willard Manning; Marshall McBean; Anne Murray; Wendy St Peter; Jay Xue; Qiao Fan; Haifeng Guo; Qi Li; Shuling Li; Yang Qiu; Suying Li; Tricia Roberts; Melissa Skeans; Jon Snyder; Craig Solid; Changchun Wang; Eric Weinhandl; Rui Zhang; Cheryl Arko; Shu-Cheng Chen; Frederick Dalleska; Frank Daniels; Stephan Dunning; James Ebben; Eric Frazier; Christopher Hanzlik; Roger Johnson; Daniel Sheets; Xinyue Wang; Beth Forrest; Delaney Berrini; Edward Constantini; Susan Everson; Paul Eggers; Lawrence Agodoa Journal: Am J Kidney Dis Date: 2007-01 Impact factor: 8.860
Authors: Barry I Freedman; Pamela J Hicks; Michele M Sale; Eric D Pierson; Carl D Langefeld; Stephen S Rich; Jianzhao Xu; Caitrin McDonough; Bart Janssen; Benito A Yard; Fokko J van der Woude; Donald W Bowden Journal: Nephrol Dial Transplant Date: 2007-01-05 Impact factor: 5.992
Authors: Stephen J Chanock; Teri Manolio; Michael Boehnke; Eric Boerwinkle; David J Hunter; Gilles Thomas; Joel N Hirschhorn; Goncalo Abecasis; David Altshuler; Joan E Bailey-Wilson; Lisa D Brooks; Lon R Cardon; Mark Daly; Peter Donnelly; Joseph F Fraumeni; Nelson B Freimer; Daniela S Gerhard; Chris Gunter; Alan E Guttmacher; Mark S Guyer; Emily L Harris; Josephine Hoh; Robert Hoover; C Augustine Kong; Kathleen R Merikangas; Cynthia C Morton; Lyle J Palmer; Elizabeth G Phimister; John P Rice; Jerry Roberts; Charles Rotimi; Margaret A Tucker; Kyle J Vogan; Sholom Wacholder; Ellen M Wijsman; Deborah M Winn; Francis S Collins Journal: Nature Date: 2007-06-07 Impact factor: 49.962
Authors: Stephen T Turner; Sharon L R Kardia; Thomas H Mosley; Andrew D Rule; Eric Boerwinkle; Mariza de Andrade Journal: J Am Soc Nephrol Date: 2006-06-14 Impact factor: 10.121
Authors: Joanlise M Leon; Barry I Freedman; Michael B Miller; Kari E North; Steven C Hunt; John H Eckfeldt; Cora E Lewis; Aldi T Kraja; Luc Djoussé; Donna K Arnett Journal: Nephrol Dial Transplant Date: 2006-12-21 Impact factor: 5.992
Authors: Fangwen Rao; Jennifer Wessel; Gen Wen; Lian Zhang; Brinda K Rana; Brian P Kennedy; Tiffany A Greenwood; Rany M Salem; Yuqing Chen; Srikrishna Khandrika; Bruce A Hamilton; Douglas W Smith; Niels-Henrik Holstein-Rathlou; Michael G Ziegler; Nicholas J Schork; Daniel T O'Connor Journal: Hypertension Date: 2007-03-12 Impact factor: 10.190