Urinary albumin excretion in families with type 2 diabetes is heritable and genetically correlated to blood pressure.

Abstract

Urinary albumin excretion in families with type 2 diabetes is heritable and genetically correlated to blood pressure. Levels of urinary albumin excretion (UAE) are used to define both the diagnosis of diabetic nephropathy and its progression. Predisposition to high blood pressure is also a risk factor for susceptibility to nephropathy, but its relationship with UAE in type 2 diabetes remains unclear. In this study, we have estimated heritabilities of UAE and blood pressure and their correlation attributable to genetic effects using 96 large families ascertained for type 2 diabetes. In these families, 630 individuals with type 2 diabetes and 639 individuals with normoglycemia were examined. All of them had a determination of UAE as the urinary albumin creatinine ratio (ACR), a convenient index of UAE, together with blood pressure and other variables, such as age, sex, and body mass index. A variance components approach was used to estimate heritability and genetic correlations for ACR and systolic and diastolic blood pressures (SBP and DBP) after adjustment for relevant covariates. In the 96 pedigrees, 6481 usable pairs of relatives were identified. In the total collection of pairs, heritability for ACR (h2 = 0.27, P < 0.001) was similar to that for blood pressure. When only pairs of diabetic relatives were analyzed (N = 1732), the estimates of heritability increased slightly for ACR (h2 = 0.31), SBP (h2 = 0.33), and DBP (h2 = 0.23). A significant genetic correlation was found between ACR and SBP (rg 0.27) and DBP (rg 0.26) in all pairs of relatives (P < 0.001). In pairs of diabetic relatives, these values were higher for SBP and DBP, 0.38 and 0.52, respectively. In families with type 2 diabetes, UAE is a heritable trait, with a heritability similar to that for blood pressure. A significant genetic correlation between UAE and blood pressure, particularly in the presence of diabetes, indicates that these traits share common genetic determinants.