Haptoglobin phenotype and diabetic nephropathy.
OBJECTIVE
To determine if the haptoglobin 2 allele is associated with an increased risk for the development of diabetic nephropathy.


METHODS
This study included 110 consecutive normotensive subjects with Type I (insulin-dependent) diabetes mellitus and Type II (non-insulin-dependent) diabetes mellitus seen in two outpatient clinics in Israel. Diabetes duration was greater than 10 years for Type I diabetes and more than 5 years for Type II diabetic subjects. Microalbuminuria was defined as urinary protein excretion of 30 to 300 mg/24 h, and macroalbuminuria was defined as urinary protein excretion of greater than 300 mg/24 h. Serum was taken from subjects for haptoglobin typing by gel electrophoresis.


RESULTS
Of the participating subjects 54 had Type I and 56 had Type II diabetes. 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 macroalbuminuria. The risk of developing macroalbuminuria was found to be greater in subjects with two haptoglobin 2 alleles (22 %) (12/55) as compared with one haptoglobin 2 allele (8 %) (3/37) or no haptoglobin 2 alleles (0%) (0/18) (p < 0.03).


CONCLUSIONS
By showing a graded risk relation to the number of haptoglobin 2 alleles in Type I and Type II diabetic subjects, these studies further support our hypothesis that the haptoglobin phenotype is a major susceptibility gene for the development of diabetic nephropathy.
Nakhoul
F M
FM
Department of Nephrology, Rambam Medical Centre, Haifa, Israel.
Zoabi
R
R
Kanter
Y
Y
Zoabi
M
M
Skorecki
K
K
Hochberg
I
I
Leibu
R
R
Miller
B
B
Levy
A P
AP
D000419:Albuminuria / Q000235:genetics; D000483:Alleles; D016009:Chi-Square Distribution; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics*; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D010641:Phenotype
D006242:Haptoglobins