Lipoprotein Lipase Ser447Ter Research Articles

The association between the genes LPL Ser447Ter, CMA1-1903A > G, FTO rs9939609 and obesity in the Rostov region from Russia

IntroductionDue to the high prevalence of diseases associated with obesity. There are several factors, including the genetic factors, it is known that the genes Fat mass and obesity-associated FTO rs9939609, the lipoprotein lipase (LPL) Ser447Ter, and the chymase 1 (CMA1) -1903A > G are associated with lipoprotein metabolism. The aim of the present investigation was to study the association of the FTO, LPL, and CMA1 genes with obesity in the children and adolescents population of the Rostov region, Russia. MethodsIn a case-control study involving 500 children and adolescents aged from 3 to 17 years, the association between the genetic polymorphisms of the FTO rs9939609, LPL Ser447Ter (rs328) and CMA1 -1903A > G (rs1800875) with the obesity was studied. The obese patients' group consisted of 300 obese children and adolescents, while the control group consisted of 200 non-obese children and adolescents. The genotyping polymorphisms for these genes was performed using PCR amplified fragments. Genetic polymorphisms in DNA samples were typed using commercial test systems NPF Liteh (Russia) with electrophoretic detection. ResultsSignificant differences (P < 0.05) were found in the frequency distribution of the AA genotype (P = 0.008; OR: 0.60; 95% CI: 0.41–0.87) and the A allele (P = 0.025; OR: 1.35; 95% CI: 1.05–1.75) of the FTO gene polymorphism rs9939609, as well as the distribution of the AA genotype (P = 0.021; OR: 1.76; 95% CI: 1.09–2.83) of the CMA1 gene polymorphism -1903A > G in the obese and control groups. A combination of FTO rs9939609, CMA1 -1903A > G of genotypes increased risks has been identified and LPL Ser447Ter of genotypes which decreased risks according to the nature of the association between the dominant and recessive models of obesity in children and adolescents. ConclusionsAn interrelation was revealed between the gene FTO rs9939609 polymorphism and the obesity, while the effect of the CMA1 -1903A > G gene on obesity is unknown, although there was a significant effect on the AA genotype of obesity among the Rostov on-don population.

Association of polymorphism genes LPL , ADRB2 , AGT and AGTR1 with risk of hyperinsulinism and insulin resistance in the Kazakh population.

Hyperinsulinism and insulin resistance are closely associated with several common diseases including type 2 of diabetes, cardiovascular diseases, and metabolic syndrome. The present study aimed to determine the association between hyperinsulinism, insulin resistance and the polymorphism of genes, including angiotensin II receptor type 1 (AGTR1), angiotensinogen (AGT), β2-adrenoreceptor (ADRB2) and lipoprotein lipase (LPL), in the Kazakh population. The design of the current research was a case-control study, involving 460 subjects (age range, 18-65 years). For every subject, plasma glucose, insulin, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, apolipoprotein B and apolipoprotein A1 were examined. Moreover, reverse transcription-quantitative PCR was conducted to detect the polymorphism genes LPL Ser447Ter, ADRB2 Gln27Glu, AGT Thr174Met and AGTR1 A1166C. Hyperinsulinism was considered when the insulin level was elevated >24.9 IU/ml. The homeostasis model assessment insulin resistance (HOMA-IR) was used to evaluate insulin resistance. The subjects were divided into hyperinsulinism (17 men and 24 women) and normal level insulin (214 men and 205 women) groups, which were also split into insulin resistance group (HOMA-IR >2.7; 80 men and 105 women) and those without insulin resistance group (151 men and 124 women). The results suggested that LPL Ser447Ter (rs328) allele G was associated with a lower risk of hyperinsulinism (P=0.037). Furthermore, polymorphisms of genes ADRB2 Gln27Glu (rs1042714), AGT Thr174Met (rs4762) and AGTR1 A1166C (rs5186) were not associated with hyperinsulinism and insulin resistance in the Kazakh population. No interaction was identified between LPL Ser447Ter, ADRB2 Gln27Glu, AGT Thr174Met and AGTR1 A1166C. Therefore, the results indicated that haplotype combinations were not associated with insulin resistance.

IMPACT OF CARDIOVASCULAR RISK GENES POLYMORPHISM IN THE DEVELOPMENT OF METABOLIC DISORDERS IN PERSONS EXPOSED TO VINYL CHLORIDE

Introduction. Xenobiotics having the ability to change the gene expression level, the degree of which depends on the genotype include vinyl chloride (VС). Its impact causes changes in lipid metabolism proatherogenic IN character. Material and methods. A prospective cohort study was conducted In 120 males contacting with VС (mean age - 46.9±0.9 years; mean experience - 17.8±0.9 years). Lipid metabolism indices were studied; the results were compared with reference values. There were evaluated the genotypes of apolipoprotein C3 (ApoC3) C3238G rs5128, apolipoprotein E (ApoE) Leu28Pro rs769452 and lipoprotein lipase (LPL) Ser447Ter rs328. The significance of intergroup differences and correspondence of genotype frequencies to the Hardy - Weinberg law were assessed by the criterion χ2. Association of alleles or genotypes with a predisposition to disorders was assessed by odds ratio (OR). Results. In workers exposed to VC, there was an increase of the concentration of proatherogenic cholesterol fraction associated with carriage of genotype G/G polymorphic variant of the gene С3238G АРОС3, protective effect against this violation has each variant allele of a polymorphic variant of the gene LPL Ser447Ter. Carriers of any variant allele C/G or G/G polymorphic variant of the gene С3238G АРОС3 increases the likelihood of violations the antiatherogenic cholesterol fraction level, and any of the variant alleles T/C or C/C polymorphic variant of the gene Leu28Pro ApoE - reduces it. Probability of an increase the triglycerides level is elevated in the presence of both alleles of polymorphic gene variant of a gene С3238G АРОС3 and decreases - in the case of carriers of both polymorphic alleles of the gene variant Leu28Pro АроЕ. The presence of any variant allele of this polymorphic variant is significant in individuals with elevated total cholesterol. Conclusion. In terms of exposure to VC the probability of development of disorders of lipid metabolism-associated with genes rs5128 and rs769452. The gene rs328 has a protective effect.

Вклад полиморфизма генов сердечно-сосудистого риска в развитие метаболических нарушений у лиц, экспонированных винилхлоридом

Introduction. Xenobiotics having the ability to change the gene expression level, the degree of which depends on the genotype include vinyl chloride (VС). Its impact causes changes in lipid metabolism proatherogenic IN character. Material and methods. A prospective cohort study was conducted In 120 males contacting with VС (mean age - 46.9±0.9 years; mean experience - 17.8±0.9 years). Lipid metabolism indices were studied; the results were compared with reference values. There were evaluated the genotypes of apolipoprotein C3 (ApoC3) C3238G rs5128, apolipoprotein E (ApoE) Leu28Pro rs769452 and lipoprotein lipase (LPL) Ser447Ter rs328. The significance of intergroup differences and correspondence of genotype frequencies to the Hardy – Weinberg law were assessed by the criterion χ 2 . Association of alleles or genotypes with a predisposition to disorders was assessed by odds ratio (OR). Results. In workers exposed to VC, there was an increase of the concentration of proatherogenic cholesterol fraction associated with carriage of genotype G/G polymorphic variant of the gene С3238G АРОС3, protective effect against this violation has each variant allele of a polymorphic variant of the gene LPL Ser447Ter. Carriers of any variant allele C/G or G/G polymorphic variant of the gene С3238G АРОС3 increases the likelihood of violations the antiatherogenic cholesterol fraction level, and any of the variant alleles T/C or C/C polymorphic variant of the gene Leu28Pro ApoE – reduces it. Probability of an increase the triglycerides level is elevated in the presence of both alleles of polymorphic gene variant of a gene С3238G АРОС3 and decreases – in the case of carriers of both polymorphic alleles of the gene variant Leu28Pro АроЕ. The presence of any variant allele of this polymorphic variant is significant in individuals with elevated total cholesterol. Conclusion. In terms of exposure to VC the probability of development of disorders of lipid metabolism-associated with genes rs5128 and rs769452. The gene rs328 has a protective effect.

The HindIII and PvuII polymorphisms of lipoprotein lipase (LPL) gene reduce the risk of ischemic stroke (IS): A meta-analysis.

Background:Lipoprotein lipase (LPL) polymorphisms were suggested to be the risk factor for ischemic stroke (IS). However, controversial results were obtained. Our objective was to investigate the association of LPL polymorphisms at Ser447Ter, HindIII (+/−), and PvuII (+/−) with IS risk.Methods:Literatures search were carried out on databases: PubMed, Web of science, the Cochrane database of system reviews, Chinese National Knowledge Infrastructure, and Embase. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to detect the relationship between LPL polymorphisms and the risk of IS.Results:No significant association was detected between LPL Ser447Ter and IS in allelic, dominant, or recessive models (P > .05). Significant lower frequencies of allelic and dominant models of LPL HindIII (+/−) and PvuII (+/−) in cases were detected (HindIII (+/−): allelic model: P = .0002, OR[95%CI] = 0.80 [0.71, 0.90]; dominant model: P = 0.003, OR[95%CI] = 0.80 [0.69, 0.92]; PvuII (+/−): allelic model: P < 0.0001, OR[95%CI] = 0.75[0.65–0.86]; dominant model: P = 0.02, OR[95%CI] = 0.67[0.48–0.93]). And the recessive model of PvuII (+/−) was significantly associated with the IS risk (P = .01, OR[95%CI] = .71[0.55–0.93]). Subgroup analysis stratified by ethnicity showed that the frequencies of allelic, dominant, and recessive models of HindIII (+/−), as well as dominant model of PvuII (+/−) were significant lower in Asian cases (HindIII (+/−): allelic model: P < .00001, OR[95%CI] = 0.69 [0.59, 0.79]; dominant model: P < .0001, OR[95%CI] = 0.69 [0.58, 0.83]; recessive model: P = .005, OR[95%CI] = 0.66 [0.50, 0.89]; PvuII (+/−): dominant model: P = .0008, OR[95%CI] = 0.66 [0.51–0.84]), but not in Caucasian cases (P > .05). In addition, the frequencies of allelic and recessive models of PvuII (+/−) significantly decreased in Caucasian cases (P < .05).Conclusion:the HindIII (+/−) and PvuII (+/−), but not the Ser447Ter might be the protective factors for IS.

Lipoprotein lipase Ser447Ter polymorphism associated with the risk of ischemic stroke: A meta-analysis

Introduction Previous studies suggested lipoprotein lipase (LPL) Ser447Ter and Asn291Ser polymorphisms were associated with the risk of ischemic heart disease, however, their effects on ischemic stroke were controversial. A meta-analysis was performed to assess the associations between these two LPL polymorphisms and the risk of ischemic stroke. Methods The electronic databases PubMed and Embase were used to identify relevant studies by two interviews independently. The pooled odds ratios (ORs) and weighted mean differences (WMD) with 95% confidence interval (CI) were estimated for the risk of ischemic stroke and the plasma lipids in various Ser447Ter genotypes respectively. A fixed or random effect model was selected for pooling data based on homogeneity test. Results 13 studies including 4,681 ischemic stroke cases and 8,516 controls were involved in this meta-analysis. Overall, LPL Ter447 variant was associated with a significantly reduced risk for ischemic stroke (OR = 0.79, 95% CI: 0.68-0.93) both in Caucasian (OR = 0.87, 95% CI: 0.77-0.97) and East-Asian (OR = 0.65, 95% CI: 0.43-0.99), whereas no significant association of Ser291 variant was observed (OR = 1.25, 95% CI: 0.96-1.63). The Ser447Ter polymorphism may be more important in association with the decreased risk of atherosclerotic stroke (OR = 0.44, 95% CI: 0.32-0.62) which derived from significantly increased high density lipoprotein cholesterol, decreased triglyceride and total cholesterol in Ter447 carriers compared with non-carriers. Conclusions This meta-analysis indicated that LPL Ser447Ter polymorphism was associated with a significant reduction in the risk of ischemic stroke, especially atherosclerotic stroke subtype in both Caucasian and East-Asian.

Apolipoprotein E (APOE) and lipoprotein lipase (LPL) gene variants and carotid atherosclerotic lesions in the oldest old: A population-based autopsy study

We investigated the association between histologically defined atherosclerotic lesions in the carotid arteries and the genetic variants of APOE and LPL in a population-based sample of Finns aged 85 or over. Post-mortem analysis of carotid arteries was performed in 240 subjects. Atherosclerotic lesions were categorized according to the modified American Heart Association criteria, and classified into four different categories: pathological intimal thickening (PIT), fibrous cap atheromas (FCA), calcified lesions (CL), and atherosclerotic burden (AB) (a combination of the other three categories). APOE ɛ4 genetic variant was associated with PIT ( p = 0.018) and AB ( p = 0.006) in the carotid arteries, and its effect was independent of the serum lipid levels. The genetic variant LPL Ser447Ter was protective against FCA ( p = 0.031) and AB ( p = 0.012), while APOE ɛ2 was protective against FCA ( p = 0.035). Our results suggest that the APOE ɛ4, ɛ2 and LPL Ser447Ter variants may have different roles in the atherosclerotic process and their effects are seen even in the oldest old population.

Lipoprotein Lipase Gene Polymorphisms and the Risk of Target Vessel Revascularization After Percutaneous Coronary Intervention

We sought to identify polymorphisms in genes that predispose to restenosis. Variations in the lipoprotein lipase (LPL) gene have been implicated in a number of pathophysiologic conditions associated with coronary heart disease. The present study examines the impact of polymorphisms in the LPL gene on restenosis (defined by target vessel revascularization [TVR]) in a large patient population undergoing percutaneous coronary intervention (PCI). A mouse model for restenosis was used to further investigate LPL's role in restenosis. The GENetic DEterminants of Restenosis (GENDER) project is a multicenter, prospective study design that enrolled 3,104 consecutive patients after successful PCI. These patients were genotyped for four different LPL gene polymorphisms. In apolipoprotein E (ApoE)*3-Leiden transgenic mice, arterial messenger ribonucleic acid (mRNA) was used to assess LPL expression during a cuff-induced restenotic process. Using multivariable analysis, carriers of the 447Ter allele of the LPL enzyme showed a lower risk of TVR compared with 447Ser homozygotes (p = 0.005). In the mouse model, LPL mRNA levels were increased 40-fold compared with control arteries at 6 h after cuff placement. The LPL C/G polymorphism (Ser447Ter), resulting in a truncation of the two C-terminal amino acids of the mature LPL protein, appears to be an important protective factor for TVR in humans. The role of LPL in this process was further established in a mouse model, where LPL expression was very strongly up-regulated in the target arterial wall, suggesting a contribution of this lipolytic enzyme to restenosis. Possibly, LPL Ser447Ter genotyping may lead to better risk stratification and tailored therapy in the prevention of restenosis after PCI.

Cholesteryl ester transfer protein TaqI B and lipoprotein lipase Ser447Ter gene polymorphisms are not associated with ischaemic stroke in Greek patients

Cholesteryl ester transfer protein (CETP) and lipoprotein lipase (LPL) are both key players in plasma lipoprotein homeostasis and, as such, genetically induced alterations in their respective activities may affect susceptibility to cerebrovascular diseases. In this study, we examined the distribution of two common polymorphisms, namely CETP TaqI B and LPL Ser447Ter in a cohort of Greek clinically diagnosed late-onset ischaemic stroke patients ( n = 98) and an ethnicity-, age- and sex-matched control group with no manifestations of vascular disease ( n = 100). Our study revealed no statistically significant differences with respect to the distribution of either polymorphism, examined separately or in combination, between the two groups.

The lipoprotein lipase Ser447Ter mutation and risk of stroke in the Chinese

Background: Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism. The Ser447Ter mutation of LPL may be associated with ischemic cerebrovascular diseases. We investigated whether the LPL variants were related to risk of strokes in Chinese Hans. Methods: We recruited 160 patients with cerebrovascular diseases (ischemic stroke, n=96; hemorrhagic stroke, n=64) and 117 age-matched controls. All subjects were Chinese Hans. Subjects were analyzed for the Ser447Ter mutation by restriction fragment length polymorphisms of the LPL gene. Results: As compared with controls, the frequency of LPL genotype CG (heterozygous Ser447Ter mutation) was lower in ischemic stroke patients (10.4% vs. 21.4%, p<0.05), and was not significantly different in hemorrhagic stroke patients (15.6% vs. 21.4%, p>0.05). The LPL G allele frequency was also lower in ischemic stroke patients (5.2%) vs. controls (10.7%, p<0.05). There was no difference between hemorrhagic stroke patients (7.8%) and controls. Serum Lp(a) concentrations were markedly lower in CG carriers than that in CC carriers in both stroke patients and the controls ( p<0.05). There was no significant difference in the concentrations of other lipids. Conclusions: Patients with ischemic stroke have a lower frequency of the LPL Ser447Ter mutation, which indicates that this mutation may have protective effect on ischemic stroke.

A common truncated variant of lipoprotein lipase in the Japanese population is characterized by pattern B phenotype.

To investigate the relationship between the lipoprotein lipase Ser447Ter (S447X) mutation, lipid profiles and risk of atherosclerotic disease, we studied two groups of Japanese subjects. These groups consisted of a dyslipidemic group (triglyceride (TG) > 1.69 mmol/l and high-density lipoprotein-cholesterol (HDL-C) < or = 0.91 mmol/l; n = 106) and a control group (TG < or = 1.69 mmol/l and HDL-C > or = 1.16 mmol/l; n = 106). All subjects in the control group were confirmed to the pattern A phenotype (normal low-density lipoprotein (LDL) pattern), and 21 individuals in this group were heterozygous for the S447X mutation, but not homozygous. In the patient group, pattern A was shown by 44 of 106 patients. The rest were of the pattern B phenotype, which is associated with an increased risk of coronary heart disease. Homozygosity was concentrated in the patient group (p < 0.05) and in those with the pattern B phenotype (p < 0.05). In contrast, heterozygosity between both groups was not statistically significant. In conclusion, heterozygous and homozygous status with respect to the LPL S447X mutation appears to have different meanings with respect to biochemical and clinical phenotypes of atherosclerosis.

Linkage and association studies of the lipoprotein lipase gene with postheparin plasma lipase activities, body fat, and plasma lipid and lipoprotein concentrations : The HERITAGE family study

Lipoprotein lipase (LPL) is responsible for the hydrolysis of triglyceride (TG)-rich lipoproteins. The aims of the present study were (1) to test for potential linkages (sib-pair method) between postheparin plasma lipase (lipoprotein and hepatic lipase) activities, body fatness, plasma lipid concentrations, and LPL polymorphisms (Ser447Ter and a tetranucleotide repeat) and microsatellite markers flanking the LPL locus (D8S261 and D8S258); and (2) to investigate associations between the LPL Ser447Ter (S447X) polymorphism and these phenotypes. Data on 190 parents and 312 adult offspring from 99 Caucasian families participating in the HERITAGE Family Study were available for this study. Data were adjusted for the effects of age within sex, and lipases, lipid variables, and abdominal visceral fat were further adjusted for fat mass. A suggestive linkage was observed only between the S447X polymorphism and very-low-density (VLDL)-apolipoprotein B (apo B) (332 sib-pairs, P = .013). The S447X polymorphism was not associated with body fat phenotypes or postheparin plasma LPL (PH-LPL) activity (men, P = .19; women, P = .47). In contrast, the X447 allele carriers had lower plasma TG (men and women, P = .01), VLDL-TG (men and women, P = .01), and VLDL-apo B (men and women, P = .009). The relationships between the X447 allele and plasma TG, VLDL-TG, and VLDL-apo B in both genders were observed in obese (body mass index [BMI] > or = 30 kg/m2) but not in normal-weight (BMI < 25 kg/m2) subjects. Thus, the S447X polymorphism of the LPL gene is not associated with body fatness and postheparin plasma lipase activities. However, the obese carriers of the X447 allele have plasma TG, VLDL-TG, and plasma cholesterol/high-density lipoprotein cholesterol (HDL-C) levels equivalent to those of normal-weight sedentary adults.