Lipoprotein Lipase ( LPL ) Gene Variation and Progression of Carotid Artery Plaque

Abstract

Background and Purpose-Coding single nucleotide polymorphisms (cSNPs) in the lipoprotein lipase (LPL) gene have been associated with lipoprotein phenotypes and vascular disease risk. We studied the association between LPL cSNPs and a novel noninvasive measure of disease, namely, cross-sectional carotid plaque area (CPA) on B-mode ultrasound. Methods-Four hundred fifty-two patients from an atherosclerosis prevention clinic had determinations of baseline and total CPA. Traditional atherosclerosis risk factors were recorded, and the LPL D9N, N291S, and S447X cSNPs were genotyped. Multiple regression analysis was used to identify determinants of CPA. Results-Minor allele frequencies for LPL D9N, N291S, and S447X were 2.8%, 0.9%, and 4.4%, respectively. There were no significant between-genotype differences in treated fasting lipids. The LPL D9N genotype was a significant predictor of both baseline CPA (Pϭ0.008) and plaque progression from baseline to 1 year later (Pϭ0.001). Heterozygotes for the N9 allele had higher mean baseline CPA and plaque progression than did LPL D9/D9 homozygotes. Conclusions-LPL D9N genotype may be a determinant of atherosclerosis as estimated by static baseline CPA and by progression of CPA.

Are Common Polymorphisms of the Lipoprotein Lipase and Human Paraoxonase-1 Genes Associated with the Metabolic Syndrome in South African Asian Indians?

“…There have been inconsistent observations made with regards to the allelic frequencies of the S447X polymorphism of the LPL gene. The frequencies for the S447X range from 4.4% in London [27] to 14% in the Mediterranean population [28]. The HuGe meta-analysis [29] reported a frequency of 9.9% for the 447X allele, with this mutation being more common in East Asians (12.2%) than Caucasians (10.3%), and is in keeping with our study findings (13%).…”

Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease

“…In association studies, although the X447 allele has been reported to be associated with a favorable lipid profile in some studies [7][8]22] the results have not been confirmed in other studies [15]. Similarly, the association of the S447X polymorphism with CAD is inconsistent [10][11][12][13][14][15][16][17][18]. In a meta analysis the association of the S447X polymorphism with TG/HDL-C and CAD was found to be small compared to three other LPL amino acid polymorphisms examined [23] or it was gender-specific [24].…”

“…Several common LPL genetic variants have been widely studied, and among them HindIII in intron 8 (T→G at position 481), and S447X in exon 9 are of particular interest because of their common occurrence (25% and 9% of the less common alleles, respectively in most populations) and their associations with plasma lipid profile [6][7][8][9][10][11] and susceptibility to CAD [10][11][12][13][14][15] in several studies, although some inconsistent results have also been reported [16][17][18]. Since the HindIII polymorphism is located in the middle of intron 8, it is not considered to be functional but rather in linkage disequilibrium with a putative functional variant.…”

Reliability of a freehand three-dimensional ultrasonic device allowing anatomical orientation “at a glance”: Study protocol for 3D measurements with Curefab CS®

“…Furthermore, precise measurements of distances, which we have proven to be feasible with Curefab CS, are a necessary condition for satisfactory application of planimetrics as the following step, which is currently the standard method for manual measurement of carotid plaque volume. Acquisition of plaque volume for monitoring carotid atherosclerotic burden therefore seems to be an achievable prospective aim with Curefab CS, and there are a multitude of previous studies showing that volume measurements and morphological characterization of carotid plaques are highly promising for non-invasive risk-stratification and genetic research [10,11,16,34] as well as evaluation of a patient's response to therapy [12,13] .…”

“…Despite its usefulness for noninvasive plaque imaging of the carotid arteries, risk stratification and genetic research [10,11] , evaluation of response to antiatherosclerotic and antihypertensive therapy [12,14] and evaluation of the influence of suspected risk factors [15,16] , the modality of three-dimensional ultrasound has not yet been established as a routine diagnostic tool on ultrasound machines. One possible explanation for this may be the fact that images of the carotid arteries comprise a scanning length of at least 4 cm, so that real-time 3-D systems cannot be used satisfactorily [1] .…”