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 (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.


CONCLUSIONS
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.
Langefeld
Carl D
CD
Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1053, USA.
Beck
Stephanie R
SR
Bowden
Donald W
DW
Rich
Stephen S
SS
Wagenknecht
Lynne E
LE
Freedman
Barry I
BI
D000368:Aged; D000419:Albuminuria / Q000208:ethnology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D044465:White People / Q000235:genetics