BACKGROUND: Elevated urinary albumin excretion and decreased glomerular filtration rate (GFR) are risk factors for cardiovascular death and end-stage renal disease in individuals with type 2 diabetes mellitus (DM). METHODS: To determine the extent of familial aggregation of GFR and urine albumin-creatinine ratio (ACR), we calculated heritability (h2) estimates by using a variance component approach. RESULTS: Among 662 participants with DM from 310 families (422 DM-concordant sibling pairs), 51.8% (n = 343) were women, mean age was 62.3 +/- 9.2 (SD) years (median, 62.6 years), diabetes duration was 10.8 +/- 7.6 years (median, 9 years), GFR was 67.6 +/- 19.0 mL/min (median, 64.7 mL/min), and urine ACR was 139.7 +/- 631.4 mg/g (median, 13.1 mg/g). Estimated h2 of GFR was 0.75 +/- 0.10 (P < 0.0001) after adjusting for age, sex, mean arterial blood pressure, medications, and hemoglobin A(1c) level. These covariates accounted for only 2% of the total phenotypic variation in log GFR. Similarly, estimated h2 of ACR was 0.46 +/- 0.12 (P < 0.0001) when adjusting for these covariates, with covariates contributing only 9% of phenotypic variation. CONCLUSION: These data provide strong evidence that among Caucasians with type 2 diabetes, GFR and urine ACR show strong familiality, suggesting that genetic factors exhibit significant influences. Given their biological and clinical importance and the similarity of these estimates with other cardiovascular disease- and DM-related traits, efforts to map genes that influence GFR and urine ACR levels should have increased importance.
BACKGROUND: Elevated urinary albumin excretion and decreased glomerular filtration rate (GFR) are risk factors for cardiovascular death and end-stage renal disease in individuals with type 2 diabetes mellitus (DM). METHODS: To determine the extent of familial aggregation of GFR and urine albumin-creatinine ratio (ACR), we calculated heritability (h2) estimates by using a variance component approach. RESULTS: Among 662 participants with DM from 310 families (422 DM-concordant sibling pairs), 51.8% (n = 343) were women, mean age was 62.3 +/- 9.2 (SD) years (median, 62.6 years), diabetes duration was 10.8 +/- 7.6 years (median, 9 years), GFR was 67.6 +/- 19.0 mL/min (median, 64.7 mL/min), and urine ACR was 139.7 +/- 631.4 mg/g (median, 13.1 mg/g). Estimated h2 of GFR was 0.75 +/- 0.10 (P < 0.0001) after adjusting for age, sex, mean arterial blood pressure, medications, and hemoglobin A(1c) level. These covariates accounted for only 2% of the total phenotypic variation in log GFR. Similarly, estimated h2 of ACR was 0.46 +/- 0.12 (P < 0.0001) when adjusting for these covariates, with covariates contributing only 9% of phenotypic variation. CONCLUSION: These data provide strong evidence that among Caucasians with type 2 diabetes, GFR and urine ACR show strong familiality, suggesting that genetic factors exhibit significant influences. Given their biological and clinical importance and the similarity of these estimates with other cardiovascular disease- and DM-related traits, efforts to map genes that influence GFR and urine ACR levels should have increased importance.
Authors: Jean W MacCluer; Marina Scavini; Vallabh O Shah; Shelley A Cole; Sandra L Laston; V Saroja Voruganti; Susan S Paine; Alfred J Eaton; Anthony G Comuzzie; Francesca Tentori; Dorothy R Pathak; Arlene Bobelu; Jeanette Bobelu; Donica Ghahate; Mildred Waikaniwa; Philip G Zager Journal: Am J Kidney Dis Date: 2010-06-19 Impact factor: 8.860
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
Authors: Madhumathi Rao; Amy K Mottl; Shelley A Cole; Jason G Umans; Barry I Freedman; Donald W Bowden; Carl D Langefeld; Caroline S Fox; Qiong Yang; Adrienne Cupples; Sudha K Iyengar; Steven C Hunt; Thomas A Trikalinos Journal: Nephrol Dial Transplant Date: 2011-05-28 Impact factor: 5.992
Authors: Amy K Mottl; Suma Vupputuri; Shelley A Cole; Laura Almasy; Harald H H Göring; Vincent P Diego; Sandra Laston; Nora Franceschini; Nawar M Shara; Elisa T Lee; Lyle G Best; Richard R Fabsitz; Jean W MacCluer; Jason G Umans; Kari E North Journal: Kidney Int Date: 2008-08-13 Impact factor: 10.612