Lipoprotein lipase gene variants relate to presence and degree of microalbuminuria in Type II diabetes

AIMS/HYPOTHESIS: Lipids and lipoproteins, particularly triglyceride rich lipoproteins, could influence the development and progression of microalbuminuria in diabetes. Lipoprotein lipase gene variants have been found to correlate with lipid/lipoprotein concentrations, especially hypertriglyceridaemia. We assessed the influence of this gene on microalbuminuria in Type II (insulin-dependent) diabetes mellitus. METHODS: Microalbuminuria was determined quantitatively in 386 sequential Type II diabetic patients by measurement of the albumin-to-creatinine ratio (ACR). DNA was analysed for two common intronic LPL single nucleotide polymorphisms (Pvu II, intron 6, and Hind III, intron 8), and three common exonic mutations (Asp(9)-Asn, exon 2, Asn(291)-Ser, exon 6, and Ser(447)-Ter, exon 9). RESULTS: Individuals with P (2) P (2) (Pvu II) and H (2) H (2) (Hind III) genotypes had significantly greater ACRs ( P(2)P(2) vs P(1)P(1)+ P(1)P(2), 5.0+/-0.5 vs 3.4+/-0.3, p=0.0004 and H(2)H(2) vs H(1)H(1)+ H(1)H(2), 4.3+/-0.4 vs 3.4+/-0.3, p=0.04). Logistic regression analysis demonstrated that only the P(2)P(2) genotype ( p=0.0004), systolic BP ( p=0.008) and creatinine ( p=0.031) were independently associated with the presence of microalbuminuria/proteinuria. P(2) homozygotes were 170% more likely to have microalbuminuria or proteinuria, O.R. 2.7 (1.6-4.5, p=0.0001), 150% more likely to have microalbuminuria, O.R. 2.5 (1.5-4.3, p=0.001), and 330% more likely to have proteinuria, O.R. 4.3 (1.6-11.4, p=0.004). There were no associations of microalbuminuria with any of the exonic polymorphisms. CONCLUSION/INTERPRETATION: Genetic variants of lipoprotein lipase correlate with presence and severity of microalbuminuria in Type II diabetes, independent of effect on serum lipids. This association is only apparent in genetic variants demonstrating greatest heterozygosity.