Lipoprotein Lipase S447X Research Articles

The influence of LPL S447X variants and obesity on lipid profile, oxidative stress, and the risk of T2DM: A case-control study.

The present study aimed to investigate the association between lipoprotein lipase (LPL) S447X polymorphism and type 2 diabetes mellitus (T2DM), obesity, lipid profile, and oxidative stress parameters in a population from the Kurdistan region of Iraq. We studied 250 adults (51% female and 49% male) aged 45-65 years in four groups, obese and normal body mass index (BMI) diabetic patients versus healthy normal BMI and obese individuals as controls. Lipid profile and oxidative stress parameters were analyzed by colorimetric assay. The LPL S447X genotypes were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism. We found that the obese diabetic group had higher levels of triglycerides (TG), cholesterol, and low-density lipoprotein-cholesterol, and lower level of high-density lipoprotein-cholesterol than other groups. Obese diabetic patients had higher anthropometric indices than nonobese diabetic patients, obese and normal BMI controls. The levels of TG and total oxidative status (TOS) were significantly lower and higher, respectively, in normal BMI controls than in obese controls. Obese diabetic patients had a lower level of total antioxidant capacity than nondiabetic obese controls. The level of TOS was lower in nondiabetic controls compared to the patient groups. Obese diabetic patients had the highest TOS and malondialdehyde levels. The LPL SX genotype was associated with decreased the risk of T2DM by 79% (odds ratio [OR] = 0.21; 95% confidence interval [CI]: 0.05-0.81, p = 0.03). Also, the presence of this genotype reduced the risk of obesity by 39% (OR = 0.61; 95% CI: 0.07-4.90, p = 0.6). In all individuals, the presence of the SX genotype was associated with significantly lower levels of fasting blood sugar (FBS) and TOS. We report the influence of obesity on lipid profile in diabetic and nondiabetic individuals and the effect of LPL SX genotype on decreased risk of T2DM and reduced levels of FBS and TOS.

Lipoprotein Lipase Gene Polymorphisms Are Associated with Myocardial Infarction Risk: A Meta-Analysis.

Aims: Many studies and researchers have reported on the genetic association between lipoprotein lipase (LPL) gene polymorphisms and myocardial infarction (MI). The results, however, have been inconclusive. Therefore, we assessed the relationship of LPL gene polymorphisms and MI risk by performing a meta-analysis. Methods: Literature was retrieved through PubMed, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and Embase databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the genetic associations between LPL gene polymorphisms and MI risk. A total of nine studies, with 10 individual groups, comprising 2785 cases and 4317 controls were used for this meta-analysis. Results: The allelic (p = 0.0003, OR [95% CI] = 0.86 [0.79-0.93]) and dominant models (p = 0.001, OR [95% CI] = 0.83 [0.73-0.93]), but not the recessive model (p > 0.05) of LPL gene showed that the HindIII variant significantly decreased the risk of MI. In addition, the allelic model (p = 0.04, OR [95% CI] = 0.71 [0.50-0.99]) for the S447X variant showed a significant decrease in the risk of MI. No association was observed between the PvuII variant and MI (p > 0.05). A subgroup analysis based on ethnicity revealed that all of the genetic models (allelic model: p < 0.00001, OR [95% CI] = 0.62 [0.51-0.77]; dominant model: p = 0.003, OR [95% CI] = 0.66 [0.50-0.87]; recessive model (p = 0.02, OR [95% CI] = 0.47 [0.25-0.88]) found an association of the HindIII polymorphism with MI in the Asian, but not in the Caucasian population (p > 0.05). Under the dominant model the HindIII SNP was also shown to be associated with MI risk in the Caucasian population (p = 0.03, OR [95% CI] = 0.87 [0.76-0.99]). In addition, the allelic (p = 0.02, OR [95% CI] = 0.75 [0.59-0.95]) and dominant models (p = 0.02, OR [95% CI] = 0.51 [0.29-0.90]) for S447X demonstrated a significantly decreased MI risk in the Caucasian, but not in the Asian population (p > 0.05). Conclusions: LPL HindIII and S447X polymorphisms, but not PvuII might be the protective factors for MI. To confirm these results, case-control studies with larger numbers of subjects need to be conducted.

Associations of the LPL S447X and Hind III Polymorphism with Type 2 Diabetes Mellitus Risk: A Meta-Analysis.

The present study was aimed to evaluate the association of lipoprotein lipase (LPL) gene (S447X and Hind III) polymorphisms and T2DM. Relevant studies were identified through systematic search PubMed, Cochrane Library, Embase, Wanfang, CNKI databases. A total of 22 studies (8 studies for LPL S447X and 14 studies for Hind III) were included. The results showed that the LPL S447X polymorphism was associated with the low risk of T2DM under dominant and allelic genetic models. Subgroup analysis by ethnicity showed that the LPL S447X polymorphism was associated with a decreased risk of T2DM in the Asian population (under dominant, heterozygous and allelic genetic models). In addition, we found that X allele carriers of S447X polymorphism is associated with low levels of TC, TG, and LDL. In subgroup analysis, Hind III polymorphism was associated with low risk of T2DM in Asian populations (under dominant, heterozygote, allele genetic models). Moreover, the carriers of H allele of Hind III have lower levels of TG, and higher levels of HDL-C. This meta-analysis demonstrated that 447X carriers and H allele in LPL gene associated with low risk of T2DM, which may due to in part to the change of serum level of TC, TG, LDL, and HDL.

Association of Candidate Gene Polymorphism with Metabolic Syndrome among Mongolian Subjects: A Case-Control Study.

Metabolic syndrome (MetS) is complex and determined by the interaction between genetic and environmental factors and their influence on obesity, insulin resistance, and related traits associated with diabetes and cardiovascular disease risk. Some dynamic markers, including adiponectin (ADIPOQ), brain-derived neurotrophic factor (BDNF), and lipoprotein lipase (LPL), are implicated in MetS; however, the influence of their genetic variants on MetS susceptibility varies in racial and ethnic groups. We investigated the association of single nucleotide polymorphism (SNP)-SNP interactions among nine SNPs in six genes with MetS’s genetic predisposition in Mongolian subjects. A total of 160 patients with MetS for the case group and 144 healthy individuals for the control group were selected to participate in this study. Regression analysis of individual SNPs showed that the ADIPOQ + 45GG (odds ratio (OR) = 2.09, p = 0.011) and P+P+ of LPL PvuII (OR = 2.10, p = 0.038) carriers had an increased risk of MetS. Conversely, G allele of LPL S447X (OR = 0.45, p = 0.036) and PGC-1α 482Ser (OR = 0.26, p = 0.001) allele were estimated as protective factors, respectively. Moreover, a haplotype containing the G-P+-G combination was related to MetS. Significant loci were also related to body mass index (BMI), systolic blood pressure (SBP), serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and fasting blood glucose (FBG), adipokines, and insulin as well as insulin resistance (p < 0.05). Our results confirm that ADIPOQ + 45T > G, LPL PvII, and PGC-1α Gly482Ser loci are associated with MetS in Mongolian subjects.

Associations between LPL gene polymorphisms and coronary artery disease: evidence based on an updated and cumulative meta-analysis.

Lipoprotein lipase (LPL) is widely linked to lipid and lipoprotein metabolism, but its effects on coronary artery disease (CAD) are not clearly elucidated. The aim of the present study was to clarify the association between LPL gene polymorphisms and CAD susceptibility. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the strength of the relationship between LPL gene polymorphisms and CAD risk. Comprehensive electronic databases, including PubMed, EMBASE, Web of Science, and the Cochrane Library, were systematically searched. A total of 45 records containing 80 eligible studies were analyzed. The results indicated an increased risk between the LPL D9N polymorphism and susceptibility to CAD in the dominant genetic model (AA + GA vs. GG: OR = 1.46, 95% CI = 1.14–1.87), whereas the LPL HindIII polymorphism showed a protective effect against CAD under all tested models (GG + GT vs. TT: OR = 0.85, 95% CI = 0.75–0.97; GG vs. TT + TG: OR = 0.62, 95% CI = 0.47–0.83; G vs. T: OR = 0.81, 95% CI = 0.71–0.92). No significant association was identified for the LPL N291S and PvuII polymorphisms. Stratification analysis by ethnicity suggested a significant correlation between the LPL S447X polymorphism and CAD susceptibility in Caucasians under the dominant and allele genetic models. In summary, our meta-analysis indicated that the LPL D9N polymorphism was associated with an increased risk of CAD, whereas the S447X and HindIII polymorphisms showed protective effects. There was no association observed between the N291S and PvuII polymorphisms and CAD risk.

Association of the lipoprotein lipase gene Ser447Ter polymorphism with hypertension and blood pressure variation: evidence from an updated meta-analysis

ABSTRACTThe polymorphism of lipoprotein lipase (LPL) gene Ser447Ter (S447X) has long been linked to hypertension and blood pressure variation, but the established data remained controversial. To better elucidate this inconsistency, a meta-analysis was conducted. We comprehensively searched electronic databases, including Pubmed, EMBASE, China National Knowledge Infrastructure (CNKI), Web of Science, for all literatures with the last update on February 2016. The strength of association was calculated by using odds ratios (ORs) and weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs). Further stratified analyses, cumulative meta-analysis analysis, and sensitivity analyses were performed. A total of 14 studies (3592 cases and 4643 controls) for hypertension and 14 studies (n = 9254) for blood pressure were included. Overall, significant associations were revealed between S447X polymorphism and hypertension risk using allelic comparison (OR = 0.86, 95%CI 0.77 to 0.96), heterozygote comparison (OR = 0.85, 95%CI 0.75 to 0.96), and the dominant model (OR = 0.85, 95%CI 0.75 to 0.96), especially in Asians. Furthermore, in subgroup analyses restricted to the population-based controls studies, the high-quality studies, and the large sample size studies, these significant associations were still observed. As for blood pressure association, significant reductions of systolic blood pressure (WMD = −1.25 mmHg, 95%CI −2.25 to −0.25 mmHg) and diastolic blood pressure (WMD = −1.91 mmHg, 95%CI −3.25 to −0.56 mmHg) levels were found using dominant model. No publication bias was observed in any comparison model. Therefore, current meta-analysis suggested that the LPL S447X polymorphism is likely to be a protective factor in the development of hypertension.

Relationship of lipoprotein lipase gene variants and fasting triglyceride levels in a pediatric population: The CASPIAN-III study.

Lipoprotein lipase (LPL) is one of the major enzymes responsible for the hydrolysis of triglyceride (TG)-rich lipoprotein. The effects of LPL polymorphisms on serum TG are inconsistent among different populations. This study aims to assess the TG serum concentration and distributions of three LPL single nucleotide polymorphisms (SNPs), namely D9N, HINDIII and S447X, in a nationally representative sample of Iranian adolescents. We studied the associations between SNP genotypes and TG levels in a nationally representative sample of Iranian adolescents. Genotyping was performed in 750 randomly selected participants. We compared the genotypes according to different TG levels. This study comprised 746 participants, with mean ± SD age of 14.6 ± 2.5 years. The distribution of genotypes of D9N and S447X were not significantly different according to TG levels. Regarding the HINDIII polymorphism, the distribution of GG, GT, and TT genotypes were significantly different in participants with low, borderline-high, and elevated TG (p = 0.02, 0.03, and 0.01, respectively). The mean TG was not significantly different according to the genotype distribution. In this study, most of the LPL gene variants were not significantly different in adolescents with normal and elevated TG, and the mean TG was not different in participants with various genotypes. As the first evidence from the pediatric population of the region of the Middle East and North Africa (MENA), these results might be used in international comparisons. Our findings might suggest that the high prevalence of hypertriglyceridemia in Iranian adolescents is more likely to be a result of lifestyle rather than genetic factors.

Impact of Lipoprotein Lipase Gene Polymorphism, S447X, on Postprandial Triacylglycerol and Glucose Response to Sequential Meal Ingestion.

Lipoprotein lipase (LPL) is a key rate-limiting enzyme for the hydrolysis of triacylglycerol (TAG) in chylomicrons and very low-density lipoprotein. Given that postprandial assessment of lipoprotein metabolism may provide a more physiological perspective of disturbances in lipoprotein homeostasis compared to assessment in the fasting state, we have investigated the influence of two commonly studied LPL polymorphisms (rs320, HindIII; rs328, S447X) on postprandial lipaemia, in 261 participants using a standard sequential meal challenge. S447 homozygotes had lower fasting HDL-C (p = 0.015) and a trend for higher fasting TAG (p = 0.057) concentrations relative to the 447X allele carriers. In the postprandial state, there was an association of the S447X polymorphism with postprandial TAG and glucose, where S447 homozygotes had 12% higher TAG area under the curve (AUC) (p = 0.037), 8.4% higher glucose-AUC (p = 0.006) and 22% higher glucose-incremental area under the curve (IAUC) (p = 0.042). A significant gene–gender interaction was observed for fasting TAG (p = 0.004), TAG-AUC (Pinteraction = 0.004) and TAG-IAUC (Pinteraction = 0.016), where associations were only evident in men. In conclusion, our study provides novel findings of an effect of LPL S447X polymorphism on the postprandial glucose and gender-specific impact of the polymorphism on fasting and postprandial TAG concentrations in response to sequential meal challenge in healthy participants.

Association of the Lipoprotein Lipase S447X and Neuropeptide Y Leu7Pro Genetic Polymorphisms with the Lipid Profiles of Individuals with and without Evidence of Coronary Artery Disease

Association of the Lipoprotein Lipase S447X and Neuropeptide Y Leu7Pro Genetic Polymorphisms with the Lipid Profiles of Individuals with and without Evidence of Coronary Artery Disease

Study of Common Genetic Variant S447X in Lipoprotein Lipase and Its Association with Lipids and Lipoproteins in Type 2 Diabetic Patients.

Elevated plasma triglyceride and non-esterified fatty acid concentrations may cause insulin resistance and type 2 diabetes mellitus. Lipoprotein lipase (LPL) is a rate-determining enzyme in lipid metabolism. A variant in the LPL gene has been identified which alters the penultimate amino acid Serine at 447 to a stop codon (S447X), and results in a truncated LPL molecule lacking the C-terminal dipeptide Ser-Gly. The present study was designed to evaluate the frequency of S447X variant in the LPL gene and its effect on the lipid and lipoprotein levels in type 2 diabetic subjects. The genotype frequency distributions of type 2 diabetes patients and controls were in Hardy-Weinberg equilibrium. Comparison of the genotype and allelic frequencies of S447X in subjects with type 2 diabetics compared to controls demonstrated no significant difference. In subjects with type 2 diabetics having hypertriglyceridemia (TG≥150mg/dl) compared to diabetics with TG level <150mg/dl, significant difference in genotype frequency was found among these groups, while allelic frequency of X was significantly differed. Logistic regression analysis showed the negative association of LPL S447X variant with TG and VLDL cholesterol, while no association with total cholesterol, HDL cholesterol and LDL cholesterol was found. The lipid levels except for HDL cholesterol were found to be significantly lower in carriers for S447X than wild type in diabetes group. The decreased level of TG and TG rich lipoprotein in subjects with SNP S447X in LPL, predicts anti-atherogenic activity of carriers for S447X variant in general population as well as type 2 diabetic patients.

The lipoprotein lipase S447X and cholesteryl ester transfer protein rs5882 polymorphisms and their relationship with lipid profile in human serum of obese individuals

BackgroundObesity is often associated with an alter lipid profile, e.g., raised serum triglycerides (TG) and low high-density lipoprotein (HDL) cholesterol levels, both important risk factor for cardiovascular-diseases. The aim of current study was to explore the association of a polymorphism of the lipoprotein lipase (LPL) rs328 and cholesteryl-ester-transfer-protein (CETP) rs5882 genes in relation to lipid profile in subjects with/without obesity. Subjects/methodsGenotyping was carried out in 271 individuals, (151 obese subjects and 120 non-obese). Univariate/multivariate analyses were conducted to evaluate the association of these genetic-polymorphisms with obesity and lipid components. ResultsObese subjects had a significantly (P<0.05) higher level of triglyceride (TG), blood pressure, waist-circumference and fasting-blood-glucose, and lower level of HDL-C. LPL and CETP polymorphisms were not associated with obesity in our population. However, the LPL rs328-GG-GC genotype was significantly related to a higher concentration of TG, compared to the CC wild-type; and a higher HDL-C level in the obesity-group with respect to the control group. Moreover, obese-subjects carrying the G allele of CETP had a significantly lower level of HDL-C (P<0.05) compared to those with C allele. ConclusionWe demonstrate a significant association of LPL and CETP polymorphisms with serum triglycerides and HDL-cholesterol.

The Association of Lipoprotein Lipase Genes, HindIII and S447X Polymorphisms With Coronary Artery Disease in Shiraz City.

Introduction: Several polymorphisms at the lipoprotein lipase (LPL) locus are associated with variations in LPL activity serum lipid concentrations and the risk of coronary artery disease (CAD). The aim of this study was to investigate the role of the LPL S447X and HindIII polymorphism in a sample of subjects with CAD and compare them with healthy subjects. Methods: The study enrolled 115 patients and 89 healthy subjects who were recruited from Namazi hospital in 2010-2012. The presence of two common polymorphisms of the LPL gene (HindIII and S447X) was determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis using genomic DNA. SPSS 16.0 was used for statistical analysis. Results: S447X was significantly different between the patients with CAD and the healthy subjects (P < 0.001). But HindIII was not significantly different between the patients with CAD and the healthy subjects (P = 0.741). Risk factors such as smoking, hypertension, hyperlipidemia, triglyceride (TG) and high-density lipoprotein (HDL) levels had a significant association with CAD. Conclusion: In our study, the presence of G allele S447X polymorphism increases the TG level and decrease HDL level, so it increases the susceptibility CAD. Moreover, HindIII polymorphism did not have any significant association with CAD.

Association of lipoprotein lipase gene polymorphisms with lipid profiles in atherosclerotic coronary artery disease

BackgroundCoronary artery disease (CAD) is a complex disease with well-documented genetic and environmental components. Lipoprotein lipase (LPL) is considered a potential target as the variations in the LPL gene have been implicated in a number of pathophysiologic conditions associated with CAD.ObjectivesThe aims of this study were to determine the relationship between LPL gene polymorphisms (PvuII and S447X) and lipid profiles in patients with CAD, and to determine its role in the prediction of the severity of coronary atherosclerosis.Patients and methodsA total of 100 individuals were classified by coronary angiography: 80 patients with CAD and 20 controls (normal coronary angiography). Clinical data, carotid sonography, blood lipid profiles, and LPL genotyping for PvuII and S447X using PCR-RFLP were assessed.ResultsPlasma lipid profiles and carotid intima-media thickness were significantly increased in CAD patients compared with controls. LPL polymorphisms were distributed for PvuII genotypes and alleles in CAD patients versus controls as follows: CC (2.5 vs. 15%), CT (76.25 vs. 75%), and TT (21.25 vs. 10.0%) genotypes; T (59.4 vs. 47.5%) and C (40.6 vs. 52.5%) alleles. LPL S447X genotypes and alleles showed no significant difference between CAD and controls. CT genotypes of LPL PvuII were the highest in number and percentage compared with CC and TT among the CAD patients (P<0.05). However, there was a significant decrease in the systolic and diastolic velocity in CC versus CG genotypes of S447X among CAD patients (P < 0.05). Other carotid ultrasound, lipid profiles, or coronary angiography parameters were not significant in both genotypes of LPL among CAD patients.ConclusionAtherosclerotic ischemic patients showed a higher association in the number and percent of CT genotypes of PvuII LPL that may be an important diagnostic risk biomarker and may implicate a therapeutic intervention in CAD.

Lipoprotein Lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS

BackgroundPrevious analysis clustered 1,238 individuals from the general population Genetics of Lipid Lowering Drugs Network (GOLDN) study by the size of their fasting very low-density, low-density and high-density lipoproteins (VLDL, LDL, HDL) using latent class analysis. From two of the eight identified groups (N = 251), ~75% of individuals met Adult Treatment Panel III criteria for the metabolic syndrome (MetS). Both showed small LDL diameter (mean = 19.9 nm); however, group 1 (N = 200) had medium VLDL diameter (mean = 53.1 nm) while group 2 had very large VLDL diameter (mean = 65.74 nm). Group 2 additionally showed significantly more insulin resistance (IR), and accompanying higher waist circumference and fasting glucose and triglycerides (all P < .01). Since lipoprotein lipase hydrolyzes triglyceride in the VLDL-LDL cascade, we examined whether these two patterns of lipoprotein diameter were associated with differences across two lipoprotein lipase (LPL) gene variants: D9N (rs1801177) and S447X (rs328).FindingsMixed linear models that controlled for age, sex, center of data collection, and family pedigree revealed no differences between the two groups for the D9N polymorphism (P = .36). However, group 2 contained significantly more carriers (25%) of the 447X variant than group 1 (14%; P = .04).ConclusionsThis was the first study this kind to show an association between LPL and large VLDL particle size within the MetS, a pattern associated with higher IR. Future work should extend this to larger samples to confirm these findings, and examine the long term outcomes of those with this lipoprotein diameter pattern.

Predictive role of polymorphisms in interleukin-5 receptor alpha-subunit, lipoprotein lipase, integrin A2 and nitric oxide synthase genes on ischemic stroke in type 2 diabetes—An 8-year prospective cohort analysis of 1327 Chinese patients

ObjectiveIschemic stroke is prevalent in type 2 diabetes and may be due to metabolic, vascular and inflammatory factors. Genetic variants implicated in these pathways may have joint effects on stroke risk. In this proof-of-concept study, we examined gene–gene interactions on risk of incident ischemic stroke in an 8-year prospective cohort of Chinese type 2 diabetic patients. MethodsSeventy-seven single nucleotide polymorphisms (SNPs) of 53 candidate genes for cardiovascular disease and inflammation were genotyped in 1327 patients with no past history of ischemic stroke. The association of SNPs with stroke was tested using Cox proportional hazard regression analysis. Permutation procedure was performed to control for multiple statistical comparisons. ResultsGenetic variants including A/A of IL5RA (interleukin-5 alpha subunit) -5091G>A, X/X of LPL (lipoprotein lipase) S447X, A/A of ITGA2 (integrin A2) G873A and T/T or G/T of NOS3 (endothelial nitric oxide synthase) G894T showed significant correlations with incident ischemic stroke. The hazard ratios (HR) increased with number of genetic risk factors reaching an adjusted HR (confidence interval) of 3.68 (1.78–7.62, P=4.4×10−4) in those with ≥2 genetic risk factors compared to those without. ConclusionPolymorphisms in IL5RA, LPL, ITGA2 and NOS3 genes were independently associated with ischemic stroke in Chinese diabetic population.

The S447X variant of lipoprotein lipase gene is inversely associated with severity of coronary artery disease

Hyperlipidemia is a major risk factor for coronary artery disease (CAD). Lipoprotein lipase (LPL) is an important enzyme in lipoprotein metabolism. S447X polymorphism of the LPL gene has been implicated in the pathogenesis of CAD. Carriers of X447 allele were reported to have lower triglyceride and higher high-density lipoprotein cholesterol levels as well as a reduced risk of CAD. We hypothesized that S447X gene polymorphism might have a protective effect for CAD. A total of 178 subjects (mean age 42.97 ± 6.5 years) who underwent coronary angiography for clinical indications were included in the study. The patients had been referred for evaluation of chest pain and/or abnormal stress tests, and were selected consecutively. Gensini scores were used to assess the severity of CAD; 97 patients were diagnosed with angiographically proven CAD, and 81 subjects did not display significant CAD (≥ 70%) angiographically. Genotyping of LPL S447X polymorphism was performed by real-time polymerase chain reaction amplification and fluorescent probe melting point analysis on the light cycler. The minor allele frequencies of LPL 447X allele were 11.1% and 6.2% among subjects without CAD compared with CAD subjects (P = 0.081) and 447X allele had favorable effects on lipid levels among CAD patients; 447X homozygotes and heterozygotes displayed lower total cholesterol (171 ± 37 vs 208 ± 48 mg/dl, P = 0.02), lower triglycerides (121 ± 72 vs 184 ± 86 mg/dl, P = 0.02), lower low-density lipoprotein cholesterol (102 ± 27 vs 129 ± 39 mg/dl, P = 0.03). Gensini scores were significantly lower among the heterozygotes and homozygotes of LPL 447X allele than in the LPL S447 homozygotes (15 ± 23 vs 25 ± 30, P = 0.048). S447X polymorphism of LPL gene may have a protective role for the severity of CAD. The beneficial effects of S447X polymorphism of the LPL gene may be through its favorable effects on lipid levels.

Lipid Profiles and Associated Gene Polymorphisms in Young Asian Indian Patients With Acute Myocardial Infarction and the Metabolic Syndrome

The objective of this study was to examine the association between serum lipid levels and the metabolic syndrome, together with polymorphisms in lipid-associated genes, in young Asian Indians with acute myocardial infarction (AMI). The study population comprised 492 patients who were 45 years old or younger. We assessed lipid levels and the frequencies of the cholesteryl ester transfer protein (CETP) Taq-1 B, lipoprotein lipase (LPL)S447X, -93 T/G, apolipoprotein B (APO B) 96bp ins/del, lipoprotein(a) (LP[a]) pentanucleotide repeat, and apolipoprotein E (APO) E epsilon 2/3/4 polymorphisms in relation to the metabolic syndrome using both National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and International Diabetes Federation (IDF) definitions. The metabolic syndrome as defined by the NCEP ATP III criteria was found in 301 (61%) patients and in 295 (60%) patients according to the IDF criteria. Hypercholesterolemia (64.5%), hypertriglyceridaemia (78.7%), low high-density lipoprotein cholesterol (HDL-C) (70.1%), and raised non-HDL-C (68.0%) occurred significantly more frequently in patients with the metabolic syndrome defined by the NCEP ATP III criteria. Similar results were observed for the IDF definition. A significant relationship with the LPL -93 T/G polymorphism was found, with the minor G allele occurring more frequently in patients defined by the NCEP ATP III criteria (odds ratio [OR] 2.72; 95% confidence interval [CI] 1.07-8.16; P = 0.023). The X allele of the LPL S447X polymorphism was observed less frequently in metabolic syndrome patients (OR 0.52; 95% CI 0.34-0.78; P = 0.0009). Several genotypes, including the LPL S447X, APO E3/E3, and the CETP Taq1 B2B2, were associated with favorable lipid profiles. Dyslipidemia occurred with similar frequency in young Asian Indian patients with AMI and the metabolic syndrome, irrespective of the definition used. Significant associations were observed between LPL gene polymorphisms and the metabolic syndrome. Several lipid-associated genotypes exerted a favorable effect on lipid profiles.

Genetic polymorphism of S447X lipoprotein lipase (LPL) and the susceptibility to hypertension

Introduction Lipoprotein lipase (LPL) is a rate-limiting enzyme responsible for the hydrolysis of triacylglycerol-rich lipoproteins releasing monoglycerides and free fatty acids, which are taken up by skeletal muscles and adipose tissue. S447X polymorphism in exon 9 of LPL gene on chromosome 8 p22 results from replacement of serine amino acid with a stop codon creating a restriction site. It has been hypothesized that the more common SS genotype is associated with a lower LPL activity compared with the infrequent SX/XX genotype. Objectives To investigate the effect of genetic polymorphism of LPL S447X in blood pressure and its atherogenic phenotype. Materials and Methods S447X variant genotype of LPL were determined by polymerase reaction (PCR) restriction fragment length polymorphism assay in 50 hypertensive patients and 50 normotensive as a control group. Anthropometric measurements and serum lipoproteins were also determined in both groups. Results The frequency of (SS) genotype was 78% in hypertensive group compared to 66% in normotensive group. Carrier of (SS) genotype were at higher risk of developing hypertension (OR, 1.8; 95% CI, 0.8-4.4) when compared with carrier of other genotypes. Furthermore, they showed atherogenic phenotype manifested by central obesity and dyslipidemia. Odds ratios were 1.8 and 2.6, respectively. Conclusion It was found that carriers of (SS) genotype were at high risk of developing hypertension.

Lipoprotein Lipase Mutation S447X Associated With Pancreatic Calcification and Steatorrhea in Hyperlipidemic Pancreatitis

The factors that whether and how genes involving lipid metabolism including lipoprotein lipase (LPL) and apolipoprotein CII (apo CII) influence occurrence of acute attack of pancreatitis and chronic pancreatitis is not clear. The aim of this study was to determine the association of LPL and apo CII genes with acute attack of pancreatitis and chronic pancreatitis in patients with hyperlipidemic pancreatitis (HLP) and hypertriglyceridemia (HTG). We performed genetic analysis of 134 patients in Taiwan with HTG (53 with HLP and 81 without HLP). The entire coding and intronic regions of the LPL and apo CII genes were identified with heteroduplex analytical techniques or high resolution melting analysis. All mutations were confirmed by sequencing analysis. Correlation of phenotype and genotype was also analyzed. The frequency of LPL gene mutation rates in HLP patients (17.0%, 9 of 53) was significantly higher than that without HLP attack (4.9%, 4 of 81) (P<0.0001). A total of 10.4% (14 of 134) of our HTG patients carried LPL or apo CII mutation. The most common LPL gene mutation was S447X. There is a high prevalence (77.8%) of HLP attack in HTG patients carrying S447X mutation. Multivariate analysis in HLP patients indicated that the presence of LPL mutation and episode of acute attack were independent risks for pancreatic calcification and steatorrhea. This is the first complete genetic study analyzing the association of LPL and apo CII mutation in a HLP population. LPL S447X mutation is associated with a higher risk of pancreatic calcification and steatorrhea than those previously known factors in HLP patients.

Diagnostic value of post-heparin lipase testing in detecting common genetic variants in the LPL and LIPC genes

Post-heparin lipoprotein lipase and hepatic lipase activities are used to identify primary disorders of triglyceride and HDL-cholesterol metabolism. Their ability to identify common variants in the lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes is unclear. To investigate the ability of lipase testing to detect common lipase gene variants, we included 183 patients who had undergone post-heparin lipase testing and genotyped the LPL D9N, N291S, PvuII, HindIII, and S447X and the LIPC-514CT, V73M, V133V, and N193S polymorphisms. Allele frequencies were compared with 163 controls. Polymorphisms with different allele frequencies in patients and controls or influencing lipids, were analyzed further. The diagnostic value of post-heparin lipase testing was assessed using logistic regression and receiver operating characteristic curves. We found that lipase activities did not predict the LPL D9N and N291S polymorphisms, but predicted the LPL S447X and LIPC-514CT polymorphisms. Adjusted for covariates, the area under the receiver operating characteristic curves was 0.643, 0.478, 0.686, and 0.657 for LPL D9N, N291S S447X and LIPC-514CT, respectively. On the basis of these findings, we conclude that high-LPL and low-HL activities associate with the LPL S447X and LIPC-514CT polymorphisms, but low-LPL activity was not related to LPL polymorphisms. Overall, the discriminative ability of post-heparin lipase tests in identifying carriers of common variants in the LPL and LIPC genes was limited. This indicates that conclusions on the genetic causes of lipase activities outside of the normal range should be drawn with caution.