Rare genetic variants with large effect on triglycerides in subjects with a clinical diagnosis of familial vs nonfamilial hypertriglyceridemia.

BACKGROUND: Most primary severe hypertriglyceridemias (HTGs) are diagnosed in adults, but their molecular foundations have not been completely elucidated. OBJECTIVE: We aimed to identify rare dysfunctional mutations in genes encoding regulators of lipoprotein lipase (LPL) function in patients with familial and non-familial primary HTG. METHODS: We sequenced promoters, exons, and exon-intron boundaries of LPL, APOA5, LMF1, and GPIHBP1 in 118 patients with severe primary HTG (triglycerides >500 mg/dL) and 53 normolipidemic controls. Variant functionality was analyzed using predictive software and functional assays for mutations in regulatory regions. RESULTS: We identified 29 rare variants, 10 of which had not been previously described: c.(-16A>G), c.(1018+2G>A), and p.(His80Arg) in LPL; p.(Arg143Alafs*57) in APOA5; p.(Val140Ile), p.(Leu235Ile), p.(Lys520*), and p.(Leu552Arg) in LMF1; and c.(-83G>A) and c.(-192A>G) in GPIHBP1. The c.(1018+2G>A) variant led to deletion of exon 6 in LPL cDNA, whereas the c.(-16A>G) analysis showed differences in the affinity for nuclear proteins. Overall, 20 (17.0%) of the patients carried at least one allele with a rare pathogenic variant in LPL, APOA5, LMF1, or GPIHBP1. The presence of a rare pathogenic variant was not associated with lipid values, family history of HTG, clinical diagnosis, or previous pancreatitis. CONCLUSIONS: Less than one in five subjects with triglycerides >500 mg/dL and no major secondary cause for HTG may carry a rare pathogenic mutation in LPL, APOA5, LMF1, or GPIHBP1. The presence of a rare pathogenic variant is not associated with a differential phenotype.

[Familial hypertriglyceridemia: biochemical, clinical and molecular study in a Moroccan family]. / Hypertriglycéridémie familiale : étude biochimique, clinique et moléculaire dans une famille marocaine.

Familial hypertriglyceridemia is a rare autosomal recessive inborn error of metabolism. Mutation within the LPL gene constitutes the first cause of monogenic etiology. Lipoprotein lipase (LPL) is the key enzyme in triglyceride-rich lipoproteins catabolism. Familial LPL deficiency is expressed by eruptive xanthomatosis and acute pancreatitis. We report a Moroccan case with a monstrous hypertriglyceridemia caused by LPL gene mutation. We discuss pathophysiology aspects according to available investigations data and the relevance of familial screening. The proband is a 19-year-old woman originating from the village of Taourirt (South of Morocco). She was admitted in emergency for diabetic ketoacidosis. Clinical investigations and routine laboratory tests were performed upon admission. Then lipoprotein electrophoresis and sequencing of the LPL gene were practiced. A monstrous hypertriglyceridemia up to 199 mmol/L was found. Lipoprotein electrophoresis has objectified profound disturbances on chylomicrons, VLDL and IDL. The sequencing detected a missense mutation p.S286R at homozygous state in a consanguinity context. Discovery of this LPL gene mutation is the first indigenous and documented case, never related in any other ethnic group. It constitutes a novel proof of a founder effect in the south Moroccan population. Prevalence studies with familial screening should be done for preventative action which is the only acceptable way to limit the cardiovascular and pancreatitis risks in this population where inbreeding is a general rule.

Inheritance of rare functional GCKR variants and their contribution to triglyceride levels in families.

Significant resources have been invested in sequencing studies to investigate the role of rare variants in complex disease etiology. However, the diagnostic interpretation of individual rare variants remains a major challenge, and may require accurate variant functional classification and the collection of large numbers of variant carriers. Utilizing sequence data from 458 individuals with hypertriglyceridemia and 333 controls with normal plasma triglyceride levels, we investigated these issues using GCKR, encoding glucokinase regulatory protein. Eighteen rare non-synonymous GCKR variants identified in these 791 individuals were comprehensively characterized by a range of biochemical and cell biological assays, including a novel high-throughput-screening-based approach capable of measuring all variant proteins simultaneously. Functionally deleterious variants were collectively associated with hypertriglyceridemia, but a range of in silico prediction algorithms showed little consistency between algorithms and poor agreement with functional data. We extended our study by obtaining sequence data on family members; however, functional variants did not co-segregate with triglyceride levels. Therefore, despite evidence for their collective functional and clinical relevance, our results emphasize the low predictive value of rare GCKR variants in individuals and the complex heritability of lipid traits.

Management of familial hypertriglyceridemia-induced pancreatitis during pregnancy with therapeutic plasma exchange: a case report and review of literature.

Familial severe hypertriglyceridemia (levels greater than 1000 mg/dL) is a known cause of acute pancreatitis. Pregnancy can dysregulate controlled lipid levels in women with familial hypertriglyceridemia and lead to acute pancreatitis and significant morbidity in both mother and fetus. We report a case of hypertriglyceridemia-induced pancreatitis during pregnancy that was successfully treated using therapeutic plasma exchange, resulting in delivery of a healthy preterm infant. Therapeutic plasma exchange is an effective approach to treat gestational hypertriglyceridemia-induced pancreatitis. Other treatment options include combined heparin and insulin infusion. Moreover, particular caution should be applied when interpreting the results of prothrombin time in the setting of severe hypertriglyceridemia as false elevation with testing methods could happen.

Altered relationship of plasma triglycerides to HDL cholesterol in patients with HIV/HAART-associated dyslipidemia: further evidence for a unique form of metabolic syndrome in HIV patients.

INTRODUCTION: Plasma triglycerides (TG) and HDL-C are inversely related in Metabolic Syndrome (MetS), due to exchange of VLDL-TG for HDL-cholesteryl esters catalyzed by cholesteryl ester transfer protein (CETP). We investigated the relationship of TG to HDL-C in highly-active antiretroviral drug (HAART)-treated HIV patients. METHODS: Fasting plasma TG and HDL-C levels were compared in 179 hypertriglyceridemic HIV/HAART patients and 71 HIV-negative persons (31 normotriglyceridemic (NL) and 40 hypertriglyceridemic due to type IV hyperlipidemia (HTG)). CETP mass and activity were compared in 19 NL and 87 HIV/HAART subjects. RESULTS: Among the three groups, a plot of HDL-C vs. TG gave similar slopes but significantly different y-intercepts (9.24±0.45, 8.16±0.54, 6.70±0.65, sqrt(HDL-C) for NL, HIV and HTG respectively; P<0.001); this difference persisted after adjusting HDL-C for TG, age, BMI, gender, glucose, CD4 count, viral load and HAART strata (7.18±0.20, 6.20±0.05 and 4.55±0.15 sqrt(HDL-C) for NL, HIV and HTG, respectively, P<0.001). CETP activity was not different between NL and HIV, but CETP mass was significantly higher in HIV (1.47±0.53 compared to 0.93±0.27µg/mL, P<0.0001), hence CETP specific activity was lower in HIV (22.67±13.46 compared to 28.46±8.24nmol/µg/h, P=0.001). CONCLUSIONS: Dyslipidemic HIV/HAART patients have a distinctive HDL-C plasma concentration adjusted for TG. The weak inverse relationship between HDL-C and TG is not explained by altered total CETP activity; it could result from a non-CETP-dependent mechanism or a decrease in CETP function due to inhibitors of CETP activity in HIV patients' plasma.

An increased burden of common and rare lipid-associated risk alleles contributes to the phenotypic spectrum of hypertriglyceridemia.

OBJECTIVE: Earlier studies have suggested that a common genetic architecture underlies the clinically heterogeneous polygenic Fredrickson hyperlipoproteinemia (HLP) phenotypes defined by hypertriglyceridemia (HTG). Here, we comprehensively analyzed 504 HLP-HTG patients and 1213 normotriglyceridemic controls and confirmed that a spectrum of common and rare lipid-associated variants underlies this heterogeneity. METHODS AND RESULTS: First, we demonstrated that genetic determinants of plasma lipids and lipoproteins, including common variants associated with plasma triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from the Global Lipids Genetics Consortium were associated with multiple HLP-HTG phenotypes. Second, we demonstrated that weighted risk scores composed of common TG-associated variants were distinctly increased across all HLP-HTG phenotypes compared with controls; weighted HDL-C and LDL-C risk scores were also increased, although to a less pronounced degree with some HLP-HTG phenotypes. Interestingly, decomposition of HDL-C and LDL-C risk scores revealed that pleiotropic variants (those jointly associated with TG) accounted for the greatest difference in HDL-C and LDL-C risk scores. The APOE E2/E2 genotype was significantly overrepresented in HLP type 3 versus other phenotypes. Finally, rare variants in 4 genes accumulated equally across HLP-HTG phenotypes. CONCLUSIONS: HTG susceptibility and phenotypic heterogeneity are both influenced by accumulation of common and rare TG-associated variants.

Mutations in lipoprotein lipase that block binding to the endothelial cell transporter GPIHBP1.

GPIHBP1, a glycosylphosphatidylinositol-anchored protein of capillary endothelial cells, shuttles lipoprotein lipase (LPL) from subendothelial spaces to the capillary lumen. An absence of GPIHBP1 prevents the entry of LPL into capillaries, blocking LPL-mediated triglyceride hydrolysis and leading to markedly elevated triglyceride levels in the plasma (i.e., chylomicronemia). Earlier studies have established that chylomicronemia can be caused by LPL mutations that interfere with catalytic activity. We hypothesized that some cases of chylomicronemia might be caused by LPL mutations that interfere with LPL's ability to bind to GPIHBP1. Any such mutation would provide insights into LPL sequences required for GPIHBP1 binding. Here, we report that two LPL missense mutations initially identified in patients with chylomicronemia, C418Y and E421K, abolish LPL's ability to bind to GPIHBP1 without interfering with LPL catalytic activity or binding to heparin. Both mutations abolish LPL transport across endothelial cells by GPIHBP1. These findings suggest that sequences downstream from LPL's principal heparin-binding domain (amino acids 403-407) are important for GPIHBP1 binding. In support of this idea, a chicken LPL (cLPL)-specific monoclonal antibody, xCAL 1-11 (epitope, cLPL amino acids 416-435), blocks cLPL binding to GPIHBP1 but not to heparin. Also, changing cLPL residues 421 to 425, 426 to 430, and 431 to 435 to alanine blocks cLPL binding to GPIHBP1 without inhibiting catalytic activity. Together, these data define a mechanism by which LPL mutations could elicit disease and provide insights into LPL sequences required for binding to GPIHBP1.

Iron deposits and dietary patterns in familial combined hyperlipidemia and familial hypertriglyceridemia.

Iron deposits are associated with lipid phenotype in familial hypertriglyceridemias, mainly familial combined hyperlipidemia (FCH) and familial hypertriglyceridemia (FHTG). In turn, diet plays an important role in hypertriglyceridemias although it is not known if dietary patterns are associated with iron concentration in these disorders. The objective was to determine the relationship between diet and iron deposits, measured through serum ferritin concentration, in patients with FCH and FHTG. The study was composed of 140 patients, 107 with FCH and 33 with FHTG. Subjects completed a validated 137-item food frequency questionnaire. Dividing subjects by ferritin tertiles adjusted by sex, there were no significant differences in dietary patterns except in dairy products consumption which was lower in the highest ferritin tertile. Subjects were also divided by triglycerides tertiles adjusted by sex. Those subjects in the highest tertile had lower HDL cholesterol and higher ferritin concentrations. Regarding to dietary parameters, there were significant differences in marine omega three fatty acids and vegetables presenting higher and lower consumption, respectively, those patients in the highest tertile of triglycerides. Moreover, there was not a significant correlation between dietary iron intake and any parameter, both biochemical and dietary, including ferritin concentrations. In conclusion, in patients with primary hypertriglyceridemia, triglycerides are associated with ferritin concentrations but dietary patterns are not related to iron deposits. Our results highly support the concept that the genetic mechanisms driven to hypertriglyceridemia also favor iron overload.

Serum ferritin is a major determinant of lipid phenotype in familial combined hyperlipidemia and familial hypertriglyceridemia.

Familial combined hyperlipidemia (FCH) and familial hypertriglyceridemia (FHTG) share pathogenic mechanisms and a high interaction with components of the metabolic syndrome. The metabolic syndrome associates increased serum ferritin concentration and high cardiovascular risk. The objective was to describe the frequency of iron overload and the relationship between serum ferritin and the phenotype in patients with FCH and FHTG. The study was composed of 211 consecutive unrelated patients aged at least 18 years with primary hypertriglyceridemia, 149 with FCH, and 62 with FHTG. The prevalence of the metabolic syndrome and hyperferritinemia was very high in both hypertriglyceridemic groups (51.7% and 20.1% in FCH and 62.9% and 16.1% in FHTG, respectively), without significant statistical differences between them. Serum ferritin concentration did not show any significant association with the number of metabolic syndrome criteria. Subjects in the highest tertile of ferritin concentration (ferritin >200 mug/L) presented higher concentrations of triglycerides and liver enzymes than subjects in the first tertile of ferritin concentration (ferritin <90 mug/L). The highest positive correlation coefficient for triglycerides was found with ferritin in FCH and in FHTG subjects (R = 0.317 [P < .001] when combined). Ferritin was also the covariate that showed the highest independent association with triglycerides in FCH and FHTG. In contrast, ferritin was not associated with carotid intima-media thickness. In summary, serum ferritin is commonly increased in FCH and in FHTG, it is not related with the presence of metabolic syndrome, and it is highly correlated with liver enzymes.

Oligo-arthritis and type IV hyperlipoproteinemia.

The increased risk of cardiovascular mortality in patients with inflammatory joint disease indicates a need for routine investigations to detect conventional cardiovascular risk factors. These investigations may provide the classification of the disease. We report a case of oligoarticular arthritis with type IV hyperlipoproteinemia, a condition of which only 15 cases are described in the literature. The patient had oligoarthritis, laboratory signs of severe inflammation, and type IV hyperlipoproteinemia (triglycerides, 24.6 mmol/L; and total cholesterol, 10.7 mmol/L). The clinical and laboratory test abnormalities resolved under fenofibrate therapy.

Distribution and effect of apo A-IV genotype on plasma lipid and apolipoprotein levels in a Chinese population.

OBJECTIVES: Hypertriglyceridaemia has been recognized as an independent risk factor for the development of coronary heart disease. Apolipoprotein A-IV (apo A-IV) plays an important role in the metabolism of TG-rich lipoproteins and HDL. However, the role of the polymorphism of the apo A-IV gene in hyperlipidaemia remains to be fully determined. The impact of the genetic variant in the apolipoprotein A-IV gene on lipid risk factor profiles for coronary heart disease was examined in Chinese patients with type-IV hyperlipoproteinaemia (HTG) and in healthy control individuals. METHODS: We genotyped five polymorphisms in the apo A-IV gene (codon 9, codon 347, codon 360, 3'end VNTR and Msp I sites) by direct sequencing or RFLP analysis in a Chinese population. RESULTS: The genotype frequencies in our results were significantly different from those reported in Caucasians. The polymorphic sites of codon 347 and codon 360, that have been widely studied in Western populations, were not observed in our population. The frequency of the G allele at codon 9 in HTG subjects was higher than that in healthy controls (P < 0.05). Serum apolipoprotein A-I (apo A-I), triglyceride (TG) and low-density lipoprotein cholesterol (LDLC) levels were affected by genotypes of codon 9, Msp I and VNTR polymorphisms, respectively, with some sex-specific effects in the control or HTG group. CONCLUSION: These results suggest that codon 9, Msp I and VNTR polymorphisms in the apo A-IV gene are associated with type-IV hyperlipoproteinaemia in a Chinese population.

[Lowering plasma homocysteine with vitamins B6, B12, and folic acid. Effect on lipids concentration in patients with secondary hyperlipoproteinemia type IV, with and without Lovastatina treatment]. / Disminución de homocisteina plasmática con vitaminas B6, B12 y ácido fólico. Su efecto en la concentración de los lípidos en pacientes con hiperlipoproteinemia secundaria tipo IV, con y sin tratamiento con lovastatina.

The concentration of plasma homocysteine was diminished by the oral use of vitamins B6 (300 mg/day), B12 (250 microg/day) and folic acid (10 mg/day), and the effect was studied in the lipids of patient with hiperlipoproteinemia secondary type IV, during 120 days, in 30 patients, 45 to 70 years old, with myocardial heart attack. They were divided in group A (n=15) without treatment with Lovastatin and group B (n=15) with Lovastatin. Basal homocysteine concentration was 17.4 +/- 1.0 micromol/L and 16.7 +/- 1.0 micromol/L for the groups A and B respectively, diminishing 24% at the end of the experimental time, in both groups. Total cholesterol decreased below 220 mg/dl, while the triglycerides diminished 25.4 mg/dl and 27.0 mg/dl in groups A and B respectively, by each micromol/L of homocysteine catabolissed. Low density lipoproteins (LDL) and very low density (VLDL) diminished significantly (p < 0.005), while the high-density (HDL) increased 1.0 mg/dl in group A and 1.15 mg/dl in group B, for each micromol/L of homocysteine metabolized, lowering the coronary risk factor in 28.5% group A and 35.9% group B. We concluded that these vitamins decreased plasma homocysteine concentration, promoting the lowering of lipids and lipoprotein concentratation in this type of patients; while Lovastatin doesn't reduce homocysteine, but it had a synergic effect with the vitamins, dicreasing the lipid concentration, in group B.

Genetics of apolipoprotein B and apolipoprotein AI and premature coronary artery disease.

Increased low-density lipoprotein (LDL) and decreased high-density lipoprotein cholesterol (HDL-C) predict premature coronary artery disease, as do elevated levels of apolipoprotein B or reduced levels of apolipoprotein AI. Probands were studied of families with common genetic forms of dyslipidaemia to determine if apo B or apo AI define genetic groups and if apo B or apo AI levels relate to premature coronary artery disease risk. Elevated apo B was characteristic of familial hypercholesterolaemia, familial combined hyperlipidaemia (FCHL), and was seen in individuals with elevated Lp(a). Normal apo B levels were seen in familial hypertriglyceridaemia and in 'coronary artery disease with low-HDL cholesterol'. Apo AI levels tended to be low in FCHL and were decreased in 'coronary disease with low-HDL cholesterol'. In familial hypertriglyceraemia, even though HDL-C levels were low, normal apo AI and apo B levels were seen in the absence of premature coronary artery disease. Therefore, in genetic dyslipidaemias elevated apo B levels and reduced apo AI levels (or increased apo B/AI ratio) differ and predict premature coronary artery disease.

Disminución de homocisteína plasmática con vitaminas B6, B12 y ácido fólico. Su efecto en la concentración de los lípidos en pacientes con hiperlipoproteinemia secundaria tipo IV, con y sin tratamiento con Lovastatina / Lowering plasma homocysteine with vitamins B6, B12 and folic acid. Effect on lipids concentration in patients with secondary hyperlipoproteinemia type IV, with and without Lovastatina treatment

Se disminuyó la concentración de homocisteina plasmática mediante el uso oral de vitaminas B6 (300 mg/día), B12 (250μg/dνa) y ácido fólico (10 mg/día), y se estudió su efecto en los lípidos de pacientes con hiperlipoproteinemia secundaria tipo IV, durante 120 días, en 30 pacientes, de 45 a 70 años de edad, con infarto al miocardio. Se dividieron en grupo A (n=15) sin tratamiento con Lovastatina y grupo B (n=15) con el hipolipemiante. La homocisteina basal fue de 17,4±1,0 μmol/L y 16,7±1,0 µmol/L para los grupos A y B respectivamente, disminuyendo un 24% al final del tiempo experimental, en ambos grupos. El colesterol total se redujo por debajo de 220 mg/dl, mientras que los triglicéridos disminuyeron 25,4 mg/dl y 27,0 mg/dl en los grupos A y B respectivamente, por cada µmol/L de homocisteina catabolizada. Las lipoproteínas de baja densidad (LDL) y de muy baja densidad (VLDL) disminuyeron significativamente (p<0,005), mientras que las de alta densidad (HDL) se incrementaron en 1,0 mg/dl para el grupo A y 1,15 mg/dl para el grupo B, por cada μmol/L de homocisteina metabolizada, disminuyendo el riesgo coronario en un 28,5% grupo A y 35,9% grupo B. Se concluye que estas vitaminas disminuyen la concentración de homocisteína plasmática, promoviendo la disminución de la concentración de lípidos y lipoproteínas en este tipo de pacientes; mientras que la Lovastatina no reduce la concentración plasmática del aminoácido; pero si ejerce un efecto sinérgico con las vitaminas en la disminución de la concentración de los lípidos, en el grupo B.

The concentration of plasma homocysteine was diminished by the oral use of vitamins B6 (300 mg/day), B12 (250μg/day) and folic acid (10 mg/day), and the effect was studied in the lipids of patient with hiperlipoproteinemia secondary type IV, during 120 days, in 30 patients, 45 to 70 years old, with myocardial heart attack. They were divided in group A (n=15) without treatment with Lovastatin and group B (n=15) with Lovastatin. Basal homocysteine concentration was 17,4±1,0 µmol/L and 16,7±1,0 µmol/L for the groups A and B respectively, diminishing 24% at the end of the experimental time, in both groups. Total cholesterol decreased below 220 mg/dl, while the triglycerides diminished 25,4 mg/dl and 27,0 mg/dl in groups A and B respectively, by each µmol/L of homocysteine catabolissed. Low density lipoproteins (LDL) and very low density (VLDL) diminished significantly (p<0,005), while the high-density (HDL) increased 1,0 mg/dl in group A and 1,15 mg/dl in group B, for each μmol/L of homocysteine metabolized, lowering the coronary risk factor in 28,5% group A and 35,9% group B. We concluded that these vitamins decreased plasma homocysteine concentration, promoting the lowering of lipids and lipoprotein concentratation in this type of patients; while Lovastatin doesn't reduce homocysteine, but it had a synergic effect with the vitamins, dincreasing the lipid concentration, in group B.

Potent capillary isotachophoresis (cITP) for analyzing a marker of coronary heart disease risk and electronegative low-density lipoprotein (LDL) in small dense LDL fraction.

BACKGROUND: The potency and usefulness of capillary isotachophoresis (cITP) for assessing whole-serum lipoprotein profiles and quantifying electronegative low-density lipoprotein (LDL) has been previously reported. METHODS AND RESULTS: A new cITP method to measure electronegative LDL in the small dense LDL fraction has been established. Both electronegative LDL and electronegative LDL in the small dense LDL fraction decreased after treatment with fenofibrate. CONCLUSIONS: This method appears to be useful for analyzing a marker of coronary heart disease risk and may be suitable for evaluating the effects of hypolipidemic agents.

[Effect of the supplementation of vitamins B12, B6 and folic acid on homocysteine and plasmatic lipids in patients with hyperlipoproteinemic secondary type IV]. / Efecto de la suplementación con las vitaminas B12, B6 y ácido fólico en los niveles de homocisteina y lípidos plasmáticos en pacientes con hiperlipoproteinemia secundaria tipo IV.

The cases of hyperlipoproteinemic secondary type IV are manifested by elevation of triglycerides, with normal or high cholesterol and lightly high homocysteine. The effect of vitamins B12, B6 and folic acid, on homocysteine and lipids, in 24 male patients, 35-68 years, with hiperlipoproteinemia secondary type IV with myocardial isquemic, and without previous treatment of hipolipemiant, was investigated. The patients were supplemented with therapeutic doses tablets of vitamin B12, 500 (microg/day); B6, (600 mg/day) and folic acid (20 mg/ day), during 120 days. Homocysteine, triglycerides, total and fractional cholesterol, at (basal), 30, 60, 90 and 120 days, were determined. Descriptive statistical analyses were applied, coefficient of correlation of Pearson and proves of "t", with a p < 0.005; the data were processed by statistical program SPSS version 8.0. The results showed a decrease in the levels of homocysteine from basal 17.1 +/- 0.7 micromol/L to 13.18 +/- 0.83 micromol/L, at the end of experimental period. The triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL) showed a reduction of (21.8 mg/dl; 8.5 mg/dl; 5.87 mg/dl; respectively) for every pmol/L of reduced homocysteine, with (p < 0.001) for triglycerides. High density lipoprotein (HDL) increased 1.1 mg/dl and coronary risk descent in 24%. We concluded that therapeutic doses of vitamins B12, B6 and folic acid, may is effective in decreased plasmatic homocysteine levels and lipids, mainly triglycerides, with a reduction of coronary risk, to these type of patients, with not collateral effects of neuropathy

[Study on apoE gene polymorphism and subclasses of serum high density lipoprotein in type IV hyperlipidemia].

OBJECTIVE: The aim of the study was to investigate apolipoprotein(apo) E polymorphism and its relationship with serum lipids and apolipoprotein, serum high density lipoprotein(HDL) subclasses in patients with type IV hyperlipidemia. METHODS: apoE genotype was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subclasses of serum HDL in 103 patients with type IV hyperlipidemia and 146 normolipidemic subjects were determined by two-dimensional gel electrophoresis in conjunction with immunodetection method. RESULTS: The apoE3/3 genotype frequency and allele epsilon 3 frequency were both the highest in the frequency distribution profiles of the type IV hyperlipidemia group and the control group. In type IV hyperlipidemia group, the genotype of apoE2 had higher serum HDL-C,apoE, HDL(2a) apoE/apoCIII ratio but lower TG/HDL-C,apoCIII, HDL(3c) levels when compared with the genotype of apoE(3) (P<0.05). In control group, the genotype of apoE(2) had higher serum TG, apoE levels and apoE/aopCIII ratio but lower HDL (3a) level when compared with the genotype of apoE(3) (P<0.05). CONCLUSION: An association of allele epsilon 2 of apoE gene with the maturation of HDL in type IV hyperlipidemia was noted in the study.