Haptoglobin phenotype and diabetic nephropathy

Aims/hypothesis. To determine if the haptoglobin S allele is associated wit h an increased risk; for the development of diabetic. nephropathy. Methods. This study included 110 consecutive normotensive subjects with Typ e I (insulin-dependent) diabetes mellitus and Tripe II (non-insulin-depende nt) diabetes mellitus seen in two outpatient clinics in Israel. Diabetes du ration was greater than 10 years for Type I diabetes and more than 5 years for Type II diabetic subjects. Microalbuminuria was defined as urinary prot ein excretion of 30 to 300 mg/24 h, and macroalbuminuria was defined at; ur inary protein excretion of greater than 300 mg/24 h, Serum was taken from s ubjects for haptoglobin typing by gel electrophoresis. Results. Of the participating subjects 54 had Type I and 56 had Type II dia betes. None (0/18) of the subjects homozygous for the haptoglobin 1 allele (1-1) showed any sign of diabetic nephropathy, as compared with 34 % (19/55 ) of subjects homozygous for the haptoglobin 2 allele (2-2) and 27 % (10/37 ) of heterozygous subjects (2-1) (p < 0.04). Of the subjects 29 showed macr oalbuminuria. The risk of developing macroalbuminuria was found to be great er in subjects with two haptoglobin 2 alleles (22 % ) (12/55) as compared w ith one haptoglobin 2 allele (8 %) (3/37) or no haptoglobin 2 alleles (0 %) (0/18) (p < 0.03), Conclusion/interpretation. By showing a graded risk relation to the number of haptoglobin. alleles in Type I and Type II diabetic subjects, these stud ies further support our hypothesis that the haptoglobin phenotype is a majo r susceptibility gene for the development of diabetic nephropathy.