Polymorphisms of angiotensin-converting enzyme and angiotensinogen genes in type 2 diabetic sibships in relation to albumin excretion rate

Familial clustering of altered albumin excretion and nephropathy risk has b een described in both type 1 and type 2 diabetes; moreover, an association of micro-macroalbuminuria and diabetic retinopathy has been recently report ed in a large number of white families with type 2 diabetes, Conflicting re ports, mainly comparing affected with unaffected unrelated subjects, have s uggested a possible role of some genotypes of the renin-angiotensin system in conferring nephropathy risk in type 2 diabetes. To examine the role of g enetic factors in influencing albuminuria in families, we studied the relat ion of angiotensin-converting enzymes (ACE) and angiotensinogen (AGN) genot ypes with albumin excretion rate in a population of affected siblings of ty pe 2 diabetic probands, We determined ACE insertion/deletion polymorphism a nd two polymorphisms of the AGN gene (T174M and M235T) in 160 families with at least one affected member. Defining proband as the patient with the lon gest known duration of diabetes, we compared the allelic distribution in di abetic probands with and without altered albumin excretion and in their sib lings. Allelic distribution of these polymorphisms was similar in the two g roups of probands, as well as in their siblings. Identity-by-State (IBS) an alysis showed a link between AGN locus and arterial hypertension in these s iblings, which was independent from the degree of renal involvement. Thus, our findings suggest that in white families with type 2 diabetes, there is no linkage between the degree of albumin excretion and ACE and AGN polymorp hisms, whereas the latter is related to arterial hypertension, as previousl y found in patients without diabetes but with essential hypertension. (C) 1 999 by the National Kidney Foundation, Inc.