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Lipoprotein lipase gene variants and progression of nephropathy in hypercholesterolaemic patients with type 2 diabetes
Author(s) -
Solini A.,
Passaro A.,
Fioretto P.,
Nannipieri M.,
Ferrannini E.
Publication year - 2004
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/j.1365-2796.2004.01332.x
Subject(s) - medicine , microalbuminuria , endocrinology , hindiii , renal function , type 2 diabetes , lipoprotein lipase , diabetes mellitus , diabetic nephropathy , nephropathy , postprandial , genotype , hepatic lipase , lipoprotein , cholesterol , biology , genetics , restriction enzyme , dna , adipose tissue , gene
. 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, Hind III 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. Design and subjects. 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). Main outcome measures. 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 (∂AER: 11 [38] vs. 4 [18] μ g 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 Hind III 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 Hind III polymorphism at the LPL locus.