Abstract
The etiology and pathogenesis of type 2 diabetes mellitus (T2DM) are not completely understood although it is often associated with other conditions such as obesity, hypertension, and dyslipidemia. Lipoprotein lipase (LPL) is a key enzyme in human lipid metabolism that facilitates the removal of triglyceride-rich lipoproteins from the bloodstream. LPL hydrolyzes the core of triglyceride-rich lipoproteins (chylomicrons and very low density lipoprotein) into free fatty acids and monoacylglycerol. To gain insight into the possible role of LPL in T2DM, nine single nucleotide polymorphisms (SNPs) of LPL were analyzed for the association with T2DM using 944 unrelated Koreans, including 474 T2DM subjects and 470 normal healthy controls. Of the nine LPL SNPs we analyzed, a significant association with multiple tests by the false discovery rate (FDR) was observed between T2DM and SNP rs343 (+13836C>A in intron 3). SNP rs343 was also marginally associated with some of T2DM-related phenotypes including total cholesterol, high density lipoprotein cholesterol (HDLc), and log transformed glycosylated hemoglobin in 470 normal controls, although no significant association was detected by multiple tests. In total, our results suggest that the control of lipid level by LPL in the bloodstream might be an important factor in T2DM pathogenesis in the Korean population.
Highlights
The normal glucose level in the blood is coordinately maintained by a complex interplay between the insulin responsiveness of key insulin target tissues and glucose-stimulated insulin secretion by pancreatic β cells (Lowell and Shulman, 2005)
We identified a total of 31 genetic variants of the Lipoprotein lipase (LPL) gene from 24 unrelated Korean subjects by sequencing (Supplemental Figure 1 and http:// www.ngri.re.kr/single nucleotide polymorphisms (SNPs)/index.jsp)
11 SNPs selected as tagging SNPs based on the LPL gene SNP associated with type 2 diabetes mellitus (T2DM) 527 criterion of pair-wise correlation coefficient, r2 ≥ 0.8 were genotyped from a total of 474 patient and 470 control subjects to discover genetic polymorphisms implicated in T2DM
Summary
The normal glucose level in the blood is coordinately maintained by a complex interplay between the insulin responsiveness of key insulin target tissues (skeletal muscle, liver, adipose tissue, kidney, and brain) and glucose-stimulated insulin secretion by pancreatic β cells (Lowell and Shulman, 2005). In type 2 diabetes mellitus (T2DM), a failure in this coordination causes insulin resistance or insufficient insulin secretion by the pancreas, leading to high blood glucose levels (Alberti and Zimmet, 1998). Deviations from normal levels of fats in the blood (dyslipidemia) are consistently associated with T2DM. Dyslipidemia associated with T2DM is characterized by high levels of both plasma triglycerides (TGs) and very low density lipoprotein (VLDL) and low levels of high density lipoprotein (HDL) (Taskinen, 2003).
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