The common mutations in the lipoprotein lipase gene in Italy: effects on plasma lipids and angiographically assessed coronary atherosclerosis

The present study evaluated the role of the common lipoprotein lipase (LPL) mutations on the risk of dyslipidemia and coronary atherosclerosis in an Italian population. Cohorts of 632 patients undergoing coronary angiography, as well as 191 healthy controls, were screened by a combination of PCR and restriction enzyme digestion. In the pooled population, the frequencies of LPL D9N and N291S were 4.1%, with no homozygous carriers, whereas that of LPL S447X was 21% with 19.6% heterozygous and 1.4% homozygous carriers. Compared to non-carriers, LPL N291S carriers showed higher plasma triglycerides (TG) (p < 0.03) and increased risk of high TG phenotype (odds ratio [OR] 2.49, 95% Cl 1.06-5.81; p < 0.03). When this LPL mutation was associated with high body mass index (BMI) ( > 25 Kg/m2) or fasting, plasma insulin (> 10.6 mU ml(-1)) significantly reduced HDL-C levels were also observed. Carriers of the S447X mutation presented with higher HDL-C concentrations (p < 0.05) as compared to non-carriers; they also showed a significantly reduced risk of high TG/low HDL-C dyslipidemia (OR 0.34, 95%, Cl 0.12-0.99; p < 0.05). The favourable effect of the LPL S447X variant was even more pronounced in lean subjects and in those with low insulin levels. No significant influence on plasma lipids by the LPL D9N was observed. None of LPL variants was a significant predictor of angiographically assessed coronary atherosclerosis. At most, the risk was borderline, increased in N291S carriers and possibly decreased in S447X carriers.     

Association of lipoprotein lipase S447X, apolipoprotein E exon 4, and apoC3 -455T>C polymorphisms on the susceptibility to diabetic nephropathy

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. In DN patients, triglyceride (TG) level is elevated and lipoprotein lipase (LPL) activity, which hydrolyzes TG, is decreased. The LPL S447X and apolipoprotein E (APOE) exon 4 polymorphisms affect TG levels, and the APOC3 -455T>C polymorphism affects LPL activity. Our aim was to examine the association of these polymorphisms with nephropathy in type 2 diabetes. We examined these polymorphisms in a case-control study of type 2 diabetic patients including 374 with DN and 392 without DN. LPL 447X-containing genotypes (447X+) were significantly decreased in DN patients [18.6 vs 25.6%, odds ratio (OR) = 0.66, p = 0.02], as were APOE epsilon3/epsilon3 genotypes (64.8 vs 73.1%, OR = 0.68, p = 0.01). In addition, combinations of genotypes [APOE epsilon3/epsilon3 and LPL 447X+ (OR = 0.56), APOC3 CC and LPL 447X+ (OR = 0.31), APOE epsilon3/epsilon3 and APOC3 CC (OR = 0.61] were protective for DN compared with the most common combination of the respective polymorphisms. Our findings suggest the importance of interactions among lipid genes in modulating the risk of DN.     

A common truncation variant of lipoprotein lipase (Ser447X) confers protection against coronary heart disease: the Framingham Offspring Study

Genetic variation at the lipoprotein lipase (LPL) locus has been shown to influence plasma lipids and to modulate risk of coronary heart disease (CHD). Recently, we found that the most frequent variant at this locus, involving a C-terminal truncation of two amino acids (Ser447X), was associated with both higher LPL activity and high density lipoprotein cholesterol (HDL-C) in patients with CHD. However, the impact of this S447X variant on lipids and CHD in the general population was hitherto unknown. We, therefore, analyzed a total of 1114 men and 1144 women randomly ascertained from the Framingham Offspring Study (FOS) for the presence of this LPL variant. Carrier frequency of the S447X allele was 17%, and in men carrier status was associated with higher total cholesterol (delta = 6.2 mg/dl, p = 0.03). higher HDL-C (delta = 2.3 mg/dl, p = 0.01), and lower triglyceride (TG) levels (delta = -19.4 mg/dl, p = 0.02). Moreover, in men, the S447X allele conferred significant protection against CHD (odds ratio: 0.43; p = 0.04). These effects on lipids and CHD were not seen in women. Our study represents the first report on the impact of this mutation on CHD in men from the general population, and we conclude, therefore, that the S447X variant may confer significant protection against high TG levels, low HDL-C, and premature CHD in these subjects.     

Variation in the lipoprotein lipase gene influences exercise-induced left ventricular growth

The adult heart relies predominantly on fatty acids (FA) for energy generation, and defects in FA catabolism cause dramatic left ventricular (LV) growth in early age. Since lipoprotein lipase (LPL) is the key enzyme in plasma triglyceride catabolism and is highly expressed in the myocardium, we investigated an association between the functional LPL gene serine 447 stop (S447X) variant and exercise-induced LV growth. The S447X variant was genotyped in 146 British Army recruits undergoing a 10-week exercise programme. Over the training period, X447 allele carriers showed less LV growth than S447 homozygotes (SS, 5.8±0.7%; SX, 2.2±1.5%; P=0.03) and a decrease in systolic blood pressure (ΔSBP: SS, 1.9±1.3 mmHg; SX, −5.7±2.2 mmHg; P=0.015). Although LPL genotype did not significantly predict LV growth with ΔSBP in statistical modelling (LPL, P=0.14; ΔSBP, P=0.06), regression analysis indicated that LPL S447X genotype effect on ΔSBP accounted for only 20% of the effect on LV growth. In multivariate analysis, LPL, peroxisome-proliferator-activated receptor alpha and angiotensin-converting enzyme genotypes were independent predictors of cardiac growth. Thus, LPL S447X genotype influenced exercise-induced changes in LV mass and SBP. Change in blood pressure accounted for a proportion of LV growth. These data suggest that increased myocardial FA availability may reduce exercise-induced LV growth. Conflict-of-interest disclosure statementNo conflict of interest exists     

Association of pre-eclampsia with common coding sequence variations in the lipoprotein lipase gene

Marked dyslipidemia may contribute to endothelial cell dysfunction in pre-eclampsia. Carriers of N291S or D9N missense mutations in the lipoprotein lipase (LPL) gene exhibit reductions in LPL activity and are predisposed to dyslipidemia and cardiovascular disease. In Caucasians, the D9N variant is in strong linkage disequilibrium with the - 93T --> G promoter variant. A fourth LPL variant, S447X, is often associated with a beneficial lipid profile. We asked if the N291S and the combination D9N/- 93T --> G variants are more prevalent, and if the S447X variant is less prevalent, in Caucasian women with pre-eclampsia as compared with normal pregnancies. DNA amplification was followed by an allele-specific oligonucleotide ligation assay. Allele frequencies were analyzed with a chi2 table and Yates' correction. The N291S variant was identified in 11.1% of pre-eclamptics as compared with 2.9% of pregnancy controls (p = 0.008). All carriers of D9N were also carriers of - 93T --> G. The D9N/ - 93T --> G combined variant was found in 7.1% of pre-eclamptics as compared with 1.4% of pregnancy controls (p = 0.02). No individuals were carriers of both N291S and D9N/ - 93T --> G. Thus, 18.2% of pre-eclamptics had either of these LPL mutations compared with 4.3% of pregnancy controls (and 4.4% of population controls). The frequency of the S447X variant did not differ among groups. We conclude that carriers of N291S or combined D9N/ - 93T --> G mutations in the LPL gene are at substantially increased risk of pre-eclampsia.     

脂蛋白脂酶S447X及HindⅢ多态性与原发性高血压代谢综合征血脂异常的关系

目的探讨原发性高血压患者中脂蛋白脂酶(lipoprotein lipase,LPL)第9外显子S447X突变及第8内含子HindⅢ多态性与代谢综合征血脂异常的关系。方法选择上海社区两周内未服用任何抗高血压药物的原发性高血压患者983例,按是否存在代谢综合征高甘油三酯和(或)低高密度脂蛋白．胆固醇分为血脂异常组和血脂正常组,应用聚合酶链反应-限制性片段长度多态技术进行LPL基因S447X及HindⅢ多态性检测。结果LPL,基因两位点间存在连锁不平衡,主要存在3种单元型：H^ S、H^-S和H^-X,与H^ S单元型相比,H^-X单元型发生血脂异常的男性OR值为0．537(95％CI：0．328～0．880),女性OR值无统计学意义;而H^-S单元型与女性血脂异常的OR值为0．535(95％CI：0．297～0．961)。LPL基因多态性与血脂谱水平的关系显示,与H^ S单元型相比,H^-X单元型男女性甘油三酯、Log(TG／HDL—C)显著降低,女性高密度脂蛋白-胆固醇水平显著升高;而H^-S单元型对血脂水平的影响无统计学意义。与H^-S单元型相比,女性H^-X单元型高密度脂蛋白．胆固醇水平显著升高、Log(TG／HDL-C)水平显著降低。结论LPL基因S447X突变与HindⅢ多态性存在连锁不平衡,H^-X单元型可能是代谢综合征血脂异常的保护因素,即H^-X单元型可能与血清甘油三脂水平显著降低,高密度脂蛋白-胆固醇水平显著升高有关。     

No association between the lipoprotein lipase S447X polymorphism and Alzheimer's disease

Results from various genetic association studies of the lipoprotein lipase (LPL) S447X polymorphism and Alzheimer's disease (AD), range from a statistically significant negative association of clinically examined patients to a non-significant but consistent trend for under-representation of the X447 allele in neuropathologically confirmed subjects. In this report we have compared the distribution of the above polymorphism in an independent group of clinically diagnosed AD patients, including a subgroup where the disease was pathologically confirmed, and a spousal control group. No statistically significant differences emerged from this comparison. We conclude that LPL cannot be a major factor in pathogenesis of AD.     

The application of end user computing (EUC) for detection of lipoprotein lipase gene abnormality]

Lipoprotein lipase (LPL) is an enzyme digesting lipoprotein triglyceride (TG) in peripheral blood vessels. Most patients with LPL deficiency show very high plasma TG and low HDL-C. To establish an effective computer-based screening system to identify individuals with genetic LPL disorders, we selected 50 subjects whose plasma TG was over 350mg/dl and HDL-C was lower than 35mg/dl from patients at Hamamatsu University Hospital. We applied End User Computing (EUC) of our laboratory system to select high risk subjects with LPL gene abnormalities. Polymerase chain reaction (PCR) products from LPL gene exons 2-9 were screened by single-strand conformation polymorphism (SSCP), direct DNA sequence analysis and restriction fragment length polymorphism (RFLP). We found a novel missense mutation (1223C-->G, S323C) in LPL gene exon 7 from three subjects. By PCR-mediated site-directed mutagenesis and restriction digestion, the three subjects were found to be heterozygous. In addition, we identified two other common mutations in Japanese employing the RFLP method. One was the 1595C-->G (S447X) in exon 9 from six subjects, two homozygous and four heterozygous individuals. The other was a mutation of intron 3 (C-->T transition) from four heterozygous subjects. Using EUC screening method, we detected genetic LPL abnormalities more easily. The frequency of the LPL gene mutation in the 50 high-risk subjects was 26%, and was estimated to be one out of 2,000 patients at our clinic. Using the EUC system to screen for LPL mutations was established to be an effective computer-based screening system to identify individuals with genetic abnormalities.     

脂蛋白脂酶Ser447Ter基因多态性与动脉硬化性脑梗死的相关研究

目的研究脂蛋白脂酶（lipoprotein lipase，LPL）Ser447Ter基因多态性与动脉粥样硬化性脑梗死（atherosclerotic cerebral infarction, CI）发病的关系及其对血脂水平、颈动脉斑块的影响。方法对166例CI患者及72名健康成人采用聚合酶链反应-限制性片段长度多态性方法检测LPL-Ser447Ter基因多态性，颈动脉超声多普勒检查颈总动脉内膜中层厚度（intima-media thickness，IMT）和颈动脉斑块（carotid artery plaque，CAP）的形状及大小。结果CI组CG＋GG基因型甘油三酯（triglyceride，TG）含量比CC基因型明显降低（P=0．1301），高密度脂蛋白胆固醇（high density lipoprotein cholesterol，HDL-C）含量明显增高（P=0．007）；对照组CG＋GG基因型TG含量比CC基因型低（P=0．041）；CI组G等位基因频率低于对照组（P=0．014）；LPLSer447Ter基因多态性与颈总动脉IMT和CAP分级无明显相关。结论LPL Ser447Ter基因多态性与血脂变化及脑梗死的关系密切，G等位基因可能引起血TG降低、HDL-C升高；G等位基因可能是脑梗死的保护基因型．     

Polymorphisms of the lipoprotein lipase gene are associated with atherosclerotic cerebral infarction in the Chinese

BACKGROUND: Lipoprotein lipase (LPL), which plays an essential role in plasma lipoprotein metabolism and transportation, appears to be a risk factor for ischemic vascular diseases. Several studies have recently reported the presence of relationship between HindIII, PvuII, Ser447Ter (C-->G) polymorphisms of LPL and ischemic vascular diseases. PURPOSE: We first studied the relationship between LPL polymorphisms and the risk of atherosclerotic cerebral infarction (CI) by detecting the frequencies of LPL HindIII, PvuII and Ser447Ter genotypes and combined genotypes in the Chinese. METHODS: We recruited 185 CI patients, confirmed by cranial computed tomography or magnetic resonance imaging/angiography, or both, and 186 control subjects. Polymerase chain reaction-restriction fragment length polymorphisms technique was used to detect HindIII, PvuII and Ser447Ter polymorphisms of the LPL gene. RESULTS: The frequencies of the H+H+ genotype and H+ allele did not differ between CI and control groups. The frequencies of the P+P+ genotype and P+ allele gene were significantly higher in the CI group (P=0.040, P=0.015). The frequencies of CG+GG genotype and G allele were lower in the CI group (P<0.001, P<0.001). In the CI group, the individuals with P+P+ genotype had a significantly higher level of plasma triglyceride (TG) and a lower level of plasma high density lipoprotein cholesterol (HDL-c). CG+GG genotypes were correlated with significantly higher levels of plasma total cholesterol (TC), HDL-c and low density lipoprotein cholesterol (LDL-c) in the CI group. The frequencies of H+/C and P+/C combined genotypes were higher in the CI group than in controls (P<0.001, P<0.001). The frequency of H+/P+/C combined genotype was significantly higher in the CI group than in controls (P<0.001). CONCLUSIONS: Our study suggests that PvuII and Ser447Ter polymorphisms are associated with lipid profile and CI.     

Physical activity modulates the effect of a lipoprotein lipase mutation (D9N) on plasma lipids and lipoproteins

We investigated interactions between a mutation (D9N) in the lipoprotein lipase (LPL) gene and physical activity, as well as other lifestyle factors, on lipid traits in a population-based sample of Dutch men and women (n = 379). We used questionnaire information to classify physical activity, alcohol consumption, and smoking habits, while overweight was defined as a body mass index (BMI) > 25 kg/m2. Non-fasting blood samples were used for the determination of lipid traits and the D9N genotype. Fifteen subjects (4%) carried the mutation. They presented with higher levels of total cholesterol, apolipoprotein (apo) B and triglycerides compared to non-carriers. While no interactions with overweight, alcohol consumption, and smoking were found, a strong interaction between the D9N mutation and physical activity became apparent. Physically inactive D9N carriers (n = 5) had considerably higher total cholesterol (+2 mmol/l, p < or = 0.0001) and apo B levels (+63 mg/dl, p < or = 0.0001) compared to non-carriers of this mutation, whereas their high-density lipoprotein (HDL)-cholesterol concentrations were lower (-0.22 mmol/l, p < 0.05). This was not the case for physically active D9N carriers (n = 10). In conclusion, a common variant of the LPL gene (D9N) adversely affects plasma lipid and lipoprotein profiles. However, the unfavorable consequences may be counteracted by physical activity.     

The Asn9 variant of lipoprotein lipase is associated with the — 93G promoter mutation and an increased risk of coronary artery disease

Two mutations in the lipoprotein lipase (LPL) gene, a T to G transition at position −93 of the proximal promoter region and an Asp9Asn substitution in exon 2, were examined in 762 Dutch males with angiographically-diagnosed coronary artery disease (CAD) and 296 healthy normolipidemic Dutch males. The two mutations exhibited strong linkage disequilibrium (D'=0.975). A significantly higher proportion of cases (4.86%) than controls (1.37%) carried the −93G/Asn9 allele (p=0.008). In the combined sample of cases and controls, adjusted mean plasma total cholesterol (TC) levels were significantly higher in −93G/Asn9 carriers (6.20±0.13 mmol/l) than in non-carriers (5.93±0.03 mmol/l; p=0.048), while mean high-density lipoprotein cholesterol (HDL-C) levels were lower in carriers (0.88±0.03 mmol/l) than in non-carriers (0.98±0.01 mmol/l; p=0.002). There was a trend towards higher triglyceride (TG) levels in carriers (1.96±0.14 mmol/l) compared with non-carriers (1.73±0.03 mmol/l) (p=0.08). Additionally, carrier frequencies in tertiles of TC, HDL-C, TG, and LPL activity, suggested an association of the −93G/Asn9 variant with higher TC and TG levels, and with lower HDL-C and LPL activity levels. Logistic regression revealed a significant odds ratio (OR) for the combined −93G/Asn9 genotype in CAD cases relative to controls (OR: 5.36; 95% CI: 1.57–18.24), with age, body mass index (BMI), smoking, and plasma total- and HDL-cholesterol levels included in the model. In conclusion, we show that the LPL Asp9Asn mutation is in non-random association with a T→G substitution at position −93 of the proximal promoter region and that the combined −93G/Asn9 genotype predisposes to decreased HDL-C levels and an increased risk of CAD.     

Two common mutations (D9N, N291S) in lipoprotein lipase: a cumulative analysis of their influence on plasma lipids and lipoproteins in men and women

We assessed the effect of two common mutations in the lipoprotein lipase gene (LPL), D9N and N291S, which have been shown to modulate plasma lipids in a wide spectrum of patients. A total of 1114 men and 1 144 women from the Framingham Offspring Study (FOS) were analyzed for these two LPL variants. Subsequently, the association with fasting plasma lipids and risk of coronary artery disease (CHD) was determined. We extended our study by calculating weighed means of lipids and lipoproteins in carriers and non-carriers for these LPL mutations in patients with genetic dyslipidemias, CHD patients and healthy controls. In the FOS sample, the D9N and N291S alleles were associated with lower high-density lipoprotein-cholesterol (HDL-C) (delta = - 0.07 mmol/ 1, p = 0.03) and a trend towards increased triglycerides (delta = 0.25 mmol/ 1, p = 0.07). In women, a trend towards the high triglyceride, low HDL-C phenotype was evident (delta = - 0.02 mmol/1 for HDL-C and delta = 0.14 mmol/l for triglycerides, respectively). Cumulative analysis of other studies of male carriers of the D9N and N291S revealed higher levels of triglycerides (D291N; 2.60(1.85) mmol/l vs. 1.62(1.18) mmol/l: p < 0.0001) (D9N; 1.94 (1.19) mmol/l vs. 1.74(1.17) mmol/l: p < 0.001) and lower HDL-C (N291S; 1.04(0.32) mmol/l vs. 1.15(0.28) mmol/l: p < 0.0001) (D9N; 1.08(0.24) mmol/l vs. 1.16(0.28) mmol/l: p < 0.0001). In females, results differed with higher TG levels (N291S; 1.70(0.99) mmol/l vs. 1.10(0.63) mmol/l: p < 0.001) (D9N; 1.08(0.76) mmol/l vs. 0.96(0.51) mmol/l: p < 0.01) and lower HDL-C levels (N291S; 1.27(0.33) mmol/l vs. 1.51(0.32) mmol/l: p < 0.0001); however, the HDL-C levels for D9N carriers were similar to non-carriers (D9N; 1.52(0.29) mmol/l vs. 1.53(0.35) mmol/l: p = 0.83). Our data provide evidence that common variants of the LPL gene are significant modulators of lipid and lipoprotein levels in both men and women.     

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.     

妊高征与脂蛋白酯酶基因Ser447-Thr多态性与血脂指标关系

目的探讨妊娠高血压综合征与脂蛋白酯酶(LPL)Ser447-Thr基因多态性的关系．方法运用多聚酶链反应一限制性内切酶片段长度多态性技术(PCR-RFIP)检测54例妊高征患者，100例正常妊娠妇女LPL Ser447-Thr基因多态性．结果妊高征组的TG、TG／HDL-C水平明显高于对照组，3种基因型频率与对照组相比差异无显著性．结论LPL Ser447-Thr突变可能不是构成妊高征的独立遗传性危险因子。     

Association between variants of lipoprotein lipase and coronary heart disease in a Tunisian population

Objective

Coronary artery disease (CAD) is a complex multifactorial disease due to the interaction of multiple genes variations and environmental factors. Genetic variants of lipoprotein lipase (LPL), a key enzyme in the hydrolysis of triglyceride rich particles, may contribute to CAD. We analysed here the frequency of LPL variants (p.Asp9Asn, p.Asn291Ser and p.Ser447X) in a Tunisian population as well as their association with circulating lipid level and risk of CAD.

Patients and methods

LPL variations were investigated by PCR-RFLP and lipid parameters were measured in 135 patients and 109 controls.

Results

The frequency of the p.Asp9Asn variation was 10.37% in CAD patients versus 3.66% in controls. The frequency for the p.Ser447X variation was 8.8% in CAD patients versus 13.7% in controls. There was no significant association between these two variants and CAD. The p.Asn291Ser mutation variation was absent in this population. In healthy subjects, heterozygote carriers of the p.Asp9Asn substitution had a significant increase level of total cholesterol (4.2 ± 0.9 mmol/L vs 5.6 ± 1.2 mmol/L; P = 0.01) and a decreased level of HDL-cholesterol (1.36 ± 0.3 mmol/L vs 0.93 ± 0.1 mmol/L; P = 0.045).

Conclusion

There was no significant association between genetic variants of the LPL gene and CAD in this Tunisian population. The very low frequency of the p.Asn291Ser variation may be an ethnic specificity of Tunisians.     

Improvement in lipid profile by nocturnal hemodialysis in patients with end-stage renal disease

Dyslipidemia is associated with uremia and an increased risk of cardiovascular disease. The uremic dyslipidemia syndrome is characterized by an abnormal lipoprotein profile that results in (1) an elevation of triglyceride (TG) rich lipoproteins, very low density lipoprotein (VLDL), and intermediate density lipoprotein (IDL); (2) a reduction in high density lipoprotein (HDL) levels; and (3) a higher fraction of atherogenic, small dense low density lipoprotein (LDL). Nocturnal hemodialysis (NHD) is a home based renal replacement therapy that provides better control of uremia than conventional hemodialysis (CHD) and that may improve dyslipidemia. To test this hypothesis, we conducted a prospective cohort study of 11 patients with end-stage renal disease (ESRD) (age 38+/-3 years [mean+/-SEMI) before and after conversion from CHD to NHD. Weight, blood pressure (BP), serum hemoglobin (Hb), phosphate (PO4), and albumin (Alb) were assessed at baseline and at 3 months after conversion to NHD. Dialysis dose on CHD and NHD was assessed using equilibrated Kt/V (eKt/V). A 12 hour fasting lipid profile (total cholesterol [TC], TG, HDL, LDL, HDL/TC) was obtained once while on CHD and at 3 months after conversion to NHD. After conversion from CHD to NHD, eKt/V per session increased significantly (from 1.13+/-0.05 to 2.10+/-0.07; p < 0.05). TG level decreased significantly (from 2.05+/-0.30 to 1.01+/-0.14 mmol/L; p < 0.001), and HDL level increased significantly (from 1.17+/-0.13 to 1.65+/-0.14 mmol/L; p < 0.001). HDL/TC also increased significantly (from 0.26+/-0.03 to 0.35+/-0.02; p < 0.001). TC and LDL levels were unchanged. HDL levels increased and TG levels decreased in all patients. There was no difference in weight, Hb, and Alb. Systolic BP and PO4 were significantly lower, and there was a trend toward a reduction in cardiovascular medications. The mechanism for the improvement in lipid profile requires further study.     

重度子痫前期孕妇血清脂蛋白脂酶与血脂相关性的研究（附910例临床资料）

目的探讨脂蛋白脂酶（LPL）在子痫前期血脂代谢中的临床意义。方法回顾性分析310例重度子痫前期孕妇（子痫前期组）和300例健康晚孕妇女（晚孕组）、300例健康未孕育龄妇女（未孕组）的血脂代谢情况;检测26例子痫前期组、30例晚孕组和30例未孕组血IJPL、TG、HDL浓度。结果子痫前期组存在显著的高TG、低HDL血脂代谢异常,LPL与TG呈负相关、与HDL呈正相关。结论子痫前期存在显著的高血脂异常代谢,LPL可能通过参与异常血脂代谢而导致子痫前期发病。     

Functional variants of the lipoprotein lipase gene and the risk of preeclampsia among non-Hispanic Caucasian women

Hypertriglyceridemia is an important pathophysiologic feature of preeclampsia, a common vascular disorder of pregnancy. Three well-documented functional variants (N291S, S447X, and D9N) of the lipoprotein lipase gene were related to hypertriglyceridemia. Results from the only two studies concerning the relationship between these variants and preeclampsia risk have been inconsistent. We investigated this relationship in a case-control study including 144 preeclamptic and 290 normotensive pregnant women (all non-Hispanic Caucasians). We estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for maternal age, pre-pregnancy body mass index, and parity. After adjusting for covariates, women with the 291 N/S or S/S genotype had significantly increased risk of preeclampsia (OR 6.9, 95% CI 1.9-25.4) compared with women with the common 291N/N genotype. The 447 S/X or X/X genotype was not significantly associated with preeclampsia risk. The frequency of the 9N variant allele was 1.8% in controls, while this allele was not observed among cases. Haplotype 9D/291S/447S was strongly associated with higher risk of preeclampsia as compared with the most common haplotype 9D/291N/447S (adjusted OR 6.6, 95% CI 1.7-25.0). Results from our study support the thesis that abnormal lipid metabolism is important in the pathogenesis of preeclampsia.     

Effect of the APOC3 Sst I SNP on fasting triglyceride levels in men heterozygous for the LPL P207L deficiency

Lipoprotein lipase (LPL) plays a major role in triglyceride (TG)-rich lipoprotein catabolism. A mutation at codon 207 (P207L) in the exon 5 of the LPL gene has been associated with 50% reduction in postheparin plasma LPL activity and significant increase in plasma TG levels in heterozygous individuals with low HDL. However, heterogeneity in fasting TG concentrations among these carriers suggests that other factors may be involved in the expression of this hypertriglyceridemic state. Indeed, previous studies have shown that the rare S2 allele of the APOC3 Sst I polymorphism was associated with higher concentrations of TG levels in noncarriers of LPL defect. Therefore, we investigated the association of the APOC3 Sst I variant on fasting lipoprotein-lipid levels in a sample of 35 heterozygous men bearing the LPL P207L mutation. Genetic association analyses were performed using the two-genotype groups S1/S1 and S1/S2. The genotype S1/S2 group was characterized by greater plasma cholesterol (plasma-C, P=0.02), plasma-TG (P=0.04), very low-density lipoproteins (VLDL)-C (P=0.004), VLDL-TG (P=0.01), VLDL-apolipoprotein B (apoB) (P=0.001) levels and cholesterol/HDL-C ratio (P=0.008), as well as lower VLDL-TG/VLDL-apoB ratio compared to the S1/S1 genotype group. These results support an exacerbating effect of the APOC3 Sst I single-nucleotide polymorphism on fasting TG levels since a large number of smaller VLDL particles are observed in LPL-deficient men bearing the APOC3 S2 allele.