Heritability of GFR and albuminuria in Caucasians with type 2 diabetes mellitus

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 (h(2)) 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 112 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.