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.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.