Lipoprotein lipase gene variants and progression of nephropathy in hypercholesterolaemic patients with type 2 diabetes.
OBJECTIVE
Recent prospective studies have identified hyperlipidaemia as an independent determinant of diabetic nephropathy. Lipoprotein lipase (LPL) is a key enzyme in the postprandial processing of triglycerides and VLDL. Among a number of common sequence variants of the LPL, HindIII has been associated with coronary heart disease and, more recently, with microalbuminuria in type 2 diabetes. We evaluated the progression of renal disease in hypercholesterolaemic type 2 diabetic patients in relation to this polymorphism.


METHODS
We followed up for 4 years 65 consecutively enrolled microalbuminuric patients with type 2 diabetes; of whom 28 had hypercholesterolaemia (6.62 +/- 0.9 mmol L(-1), group A) and 37 were normocholesterolaemic (4.68 +/- 0.5 mmol L(-1), group B).


METHODS
After performing the genetic analyses, albumin excretion rate (AER) and estimated glomerular filtration rate (GFR), calculated by the simplified equation of the MDRD Study Group, were repeated every year.


RESULTS
In group A, AER increased more (deltaAER: 11 [38] vs. 4 [18] microg min(-1) per year in group B, P < 0.0001) while GFR declined faster (-3.5 +/- 2.1 vs. -2.0 +/- 1.4 mL min(-1) per year, P < 0.02). Patients homozygous for the allele + of HindIII showed a significantly faster decline of GFR and a higher increase of AER (both P = 0.0001) even after adjustment for cholesterol levels and anthropometric variables.


CONCLUSIONS
In hypercholesterolaemic type 2 diabetic patients with microalbuminuria, the renal disease has an accelerated course, particularly in those carrying the H+/H+ genotype of the HindIII polymorphism at the LPL locus.
Solini
A
A
Department of Internal Medicine, University of Pisa, Pisa, Italy.
Passaro
A
A
Fioretto
P
P
Nannipieri
M
M
Ferrannini
E
E
D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology; D003928:Diabetic Nephropathies / Q000097:blood / Q000201:enzymology*; D003930:Diabetic Retinopathy / Q000201:enzymology; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000201:enzymology*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011446:Prospective Studies
D008078:Cholesterol, LDL; D008071:Lipoprotein Lipase