Heritability of albumin excretion rate in families of patients with Type II diabetes

Abstract

Diabetic nephropathy develops in up to 30 % of patients with Type I (insulin-dependent) diabetes mellitus after 30 years duration, whereas the cumulative risk in Type II (non-insulin-dependent) diabetes mellitus varies between 25 and 50 % depending upon ethnic background and age at onset [1±3]. Although hyperglycaemia in itself represents the most important single risk factor for the development of diabetic nephropathy, genetic predisposition is also considered to have an important role. A familial clustering of diabetic nephropathy has been shown in both Type I and Type II diabetes [4±6]. Therefore an intensive search for genes which increase susceptibility to diabetic nephropathy has been initiated.For genetic studies it is essential to correctly define the phenotype as early as possible. Microalbuminuria has served this purpose as it predicts diabetic nephropathy in both Type I and Type II diabetes [7±10]. Microalbuminuria is, however, also associated with cardiovascular disease [11] and it is not entirely clear whether the same genetic mechanisms confer suscep- Diabetologia (1999) AbstractAims/hypothesis. To study whether albumin excretion rate is an inherited trait in families of patients with Type II (non-insulin-dependent) diabetes mellitus. Methods. We used three different approaches. Heritability of albumin excretion rate was studied in 267 nuclear families from the Botnia Study in Western Finland using parent-offspring regression. Albumin excretion rate was also measured in 206 non-diabetic offspring of 119 Type II diabetic parents with or without albuminuria (albumin excretion rate > 20 mg/ min). Finally, albumin excretion rate was measured in altogether 652 siblings of 74 microalbuminuric and 320 normoalbuminuric probands. To study the potential confounding effect of blood pressure, the heritability of blood pressure was estimated in 718 nuclear families.Results. Using parent-offspring regression, the heritability of albumin excretion rate was about 30 %, being the strongest from mothers to sons (35±39 % resemblance). The heritability for systolic blood pressure ranged from 10 to 20 % and for diastolic blood pressure from 10 to 27 %. Offspring of albuminuric Type II diabetic parents had higher albumin excretion rates (median 5.

Heritability and familiality of type 2 diabetes and related quantitative traits in the Botnia Study

“…As reported previously [18], there was a modest heritability for AER in all as well as in non-diabetic individuals (0.35 and 0.30 respectively).…”

Autonomic Neuropathy in Nondiabetic Offspring of Type 2 Diabetic Subjects Is Associated With Urinary Albumin Excretion Rate and 24-h Ambulatory Blood Pressure

“…Different factors (including hyperglycemia) could subsequently affect the expression of the genes and influence the progression of neuropathy. In Pima Indians (42), sib-pair analyses of genes associated with retinopathy and nephropathy identified different loci on chromosomes that could affect susceptibility to these complications, and results from studies on clustering of microalbuminuria indicate that microalbuminuria might be an inherited trait in nondiabetic family members of patients with type 2 diabetes (43,44). These results suggest that genetic factors could play a role in the pathogenesis of the features known as complications of type 2 diabetes, and they also suggest that these features can be present without diabetes.…”

Common variants in CNDP1 and CNDP2, and risk of nephropathy in type 2 diabetes

“…Familial clustering has been observed, supporting the presence of a genetic component [4,7]. Increased urinary albumin excretion is a hallmark of diabetic nephropathy and heritability for albuminuria has been estimated to be about 0.4 [7,8]. Recent genome-wide linkage scans in different ethnic groups have shown an association between diabetic nephropathy and a locus on chromosome 18q [9][10][11], which also harbours two carnosine dipeptidase (CNDP) genes, CNDP1 and CNDP2.…”