Genetic variation at the apolipoprotein gene loci contribute to response of plasma lipids to dietary change

Dietary intervention studies (from a low polyunsaturated/saturated fatty acid ratio P/S diet to a high P/S diet), carried out on a group of healthy individuals from North Karelia, Eastern Finland between 1981-1984, provided evidence that there may be a genetic component contributing to variation in response to dietary change. We have resampled blood from 107 individuals involved in the original studies and used Restriction Fragment Length Polymorphisms (RFLPs) to study the genetic contribution of variation at a number of candidate gene loci to the response to dietary change. The genes investigated in this study were the apolipoprotein (apo) genes: apo B, apo AII, apo E (protein polymorphism), apo AI-CIII-AIV gene cluster, and the LDL-receptor gene. On the basal diet the major effect of genotype on lipid traits was due to variation at the apo E gene locus; this protein polymorphism explained 14.6% of the phenotypic variance in LDL cholesterol levels and 12.7% of the phenotypic variance in total cholesterol levels. When switched to low fat high P/S diet, these effects of variation at the apo E gene locus on the phenotypic variation of LDL and total cholesterol levels disappeared. The major effect on the response to dietary change, delta, was seen on the difference in apo AI levels mediated by variation at the apo B gene locus (MspI RFLP) explaining 6.3% of the phenotypic variance in apo AI change. For the RFLPs of the apo AI-CII-AIV gene cluster, small but not significant differences on delta were found. Our results indicate that within the limits of the candidate genes studied, the major effects in response to dietary change was on apo AI levels mediated through variation at the apo B gene locus.     

Apolipoprotein E polymorphism and plasma lipid, lipoprotein, and apolipoprotein levels in Italian children.

We have investigated the effect of apolipoprotein (apo) E polymorphism on serum lipid, lipoprotein, and apolipoprotein levels in a sample of 195 children, aged 8-11 years, from Sezze, Central Italy. The relative frequencies of e2, e3, and e4 alleles were 0.062, 0.867, and 0.072, respectively. Variation at the apo E gene locus explained 5.1% of the sample variance in serum total cholesterol levels, 7.6% in low-density lipoprotein (LDL) cholesterol levels, 7.3% in apo B levels, and 14.1% in high-density lipoprotein-apo E (HDL-E) levels. The effect of the e2 allele was to lower levels of total cholesterol, LDL-cholesterol, and apo B and to raise levels of HDL-E, while the effect of the e4 allele was the opposite. Variation at the apo E gene locus was not associated with differences in serum triglyceride, HDL-cholesterol, or apo AI levels. The effects of common apo E polymorphisms and genetic variation associated with the PvuII RFLP of the apo B gene on serum apo B levels were additive, explaining 11.3% of the phenotypic variance in this sample. When the effect of apo E polymorphism on serum lipid traits was estimated in boys and girls separately, variation at the apo E gene locus explained 10.4, 13.3, 13.3, and 13.5% of the phenotypic variance in serum total cholesterol, LDL-cholesterol, apo B, and HDL-E levels, respectively, in boys, while in girls only the effect on HDL-E levels (19.3%) reached statistical significance. This study has demonstrated that genetic variations at the apo E locus contribute to the determination of serum lipid, lipoprotein, and apolipoprotein levels in youths and that the effects are gender specific.     

Role of genetic variation at the Apo AI-CIII-AIV gene cluster in determining plasma Apo AI levels in boys and girls

We have investigated the effect of the G/A substitution in the promoter region of the apolipoprotein (apo) AI gene (?75 bp) on plasma lipid, lipoprotein and apolipoprotein levels in a sample of 204 children from central Italy. The subjects included 111 boys and 93 girls, aged 8–11 years old. The frequency of the A allele was 0.19 in the total sample, and 0.21 and 0.17 in boys and girls, respectively. Using analysis of variance, we found the G/A substitution was significantly associated with plasma levels of total cholesterol, LDL cholesterol, apo B, and apo AI in boys, accounting for 7.0, 4.2, 5.3, and 4.3% of the sample variance, respectively. Individuals with an A allele had higher mean levels of these lipid traits than individuals homozygous for the G allele. A dietary intervention study had been carried out in a subset of these children, and the effect of the G/A substitution on plasma apo AI levels remained when boys changed to a low fat low cholesterol diet. However, no significant association was observed in girls between any of the lipid traits and the G/A genotypes. We have previously reported in this sample of children that the two polymorphisms detected with restriction enzyme PvuII, with variable sites in the first intron of the apo CIII gene (Pvu II–CIII) and the apo CIII–AIV intergenic region (Pvu II–AIV), were associated with significant differences on plasma apo AI levels. We found that the association reached statistical significance in boys only in this study. Taking these three polymorphisms together, the effects on plasma apo AI levels were additive in boys, accounting for 20.0% of the sample variance. Boys having the genotype GG/V^?V⁺ of the G/A substitution and the PvuII–AIV RFLP had mean apo AI levels 36 mg/dl lower than boys with the genotype GA + AA/V^?V^?. In girls, however, there was evidence of significant interaction of effects between the PvuII–AIV RFLP and the G/A substitution (P < 0.04), with the A allele being associated with higher levels of plasma apo AI only in girls having the rare allele (V⁺) of the PvuII–AIV RFLP. We conclude that genetic variation at the apo AI-CIII-AIV gene cluster is having a major impact on the determination of plasma apo AI levels in this sample of young boys, with additive effects due to functional changes at several places in this gene cluster detected directly (G/A) or in allelic association with the PvuII–CIII and PvuII–AIV polymorphisms. These effects are not modulated by diet but are modulated by other factors, possibly hormones, which are present in girls. © 1993 Wiley-Liss. Inc.     

Genetic epidemiology of differences in low-density lipoprotein (LDL) cholesterol concentration: possible involvement of variation at the apolipoprotein B gene locus in LDL kinetics

Circulating levels of low-density lipoprotein (LDL) vary considerably within and between populations, paralleled by differing coronary heart disease (CHD) mortality rates. We have previously shown that variation in the apolipoprotein (apo) B gene as associated with certain restriction fragment length polymorphisms (RFLPs) influences the metabolism of LDL in the U.K. population. To investigate a possible genetic contribution to variation in LDL levels in differing populations we have extended this original study. RFLPs of the apo B gene were determined in samples of individuals from the United Kingdom, Finland, Italy, Spain, and Africa. Significant associations of LDL fractional catabolic rate with the apo B EcoRI and XbaI RFLP genotypes were detected only in the two North European populations. In the African population sample, the XbaI RFLP displayed a significant association with LDL apo B synthesis. The data suggest that variation in the apo B gene influences the metabolism of LDL and that it is different in individuals of different ethnic background.     

Dietary monounsaturated fat activates metabolic pathways for triglyceride-rich lipoproteins that involve apolipoproteins E and C-III

BACKGROUND: Dietary monounsaturated fat (MUFA) and complex carbohydrates have different effects on triglyceride-rich lipoprotein (TRL) metabolism. OBJECTIVE: We hypothesized that apolipoprotein (apo) E and apo C-III might be involved in these dietary effects because of their crucial role in TRL metabolism. DESIGN: Twelve adults consumed, for 3 wk each, 2 isocaloric diets: first a carbohydrate-rich diet (48% complex carbohydrate, 8% MUFAs) and then a MUFA-rich diet (31% complex carbohydrate, 24% MUFAs) 12 mo later. The dietary composition of other macronutrients in the 2 diets was similar. Body weight was kept constant. Postprandial apo B kinetic studies using stable-isotope tracers were performed after each dietary intervention. Multiple VLDL, intermediate-density lipoprotein (IDL), and LDL fractions were prepared on the basis of apo E and apo C-III contents. RESULTS: The MUFA diet increased by approximately 4-6-fold, the secretion of VLDLs and IDLs containing both apo E and apo C-III (E+CIII+) (P < 0.05). These are TRLs that mostly cleared from the circulation and are minor precursors of LDL. The MUFA diet also decreased by 60% (P < 0.05) the secretion of the TRLs without apo E or apo C-III (major precursors of LDL in plasma) and decreased their flux to LDLs. Total LDL flux did not change because the MUFA diet increased the flux to LDL from E-CIII+ TRLs, a process that requires the removal of apo C-III. In addition, the MUFA diet significantly increased the TRL fractional catabolic rate by 50% and doubled the percentage of TRLs that were cleared rather than being converted to LDLs. CONCLUSION: MUFA intake activates synthetic and rapid catabolic pathways for TRL metabolism that involve apo E and apo C-III and suppresses the metabolism of more slowly metabolized VLDLs and IDLs, which do not contain these apolipoproteins.     

Apolipoprotein B-gene DNA polymorphisms (XbaI and EcoRI), serum lipids, and apolipoproteins in healthy Chinese.

The frequency of restriction fragment length polymorphisms (RFLPs) of the apolipoprotein B (apo B) gene, detected by XbaI and EcoRI, and their influence on serum lipids and apolipoproteins were studied in healthy Chinese of both sexes in Singapore. A total of 221 subjects (150 males, 71 females) were investigated for the XbaI and 159 subjects for the EcoRI polymorphisms, while serum lipids and apolipoprotein levels were available for 196 subjects. The frequency of the X2 allele was found to be significantly lower in the Chinese than that reported in Caucasians from the United Kingdom (0.09 vs. 0.51, P less than 0.001). The haplotype frequencies were also significantly different between the Chinese and Caucasians with a higher frequency of X1R1 in the former compared to the latter (0.85 vs. 0.34, P less than 0.0001). The distribution of RFLP genotypes at both of the restriction sites was at Hardy-Weinberg equilibrium in all groups. The influence of the apo B RFLPs on serum lipids and apolipoprotein levels (apo AI, AII, and B) was studied by both residual and multiple regression analyses considering age, sex, body mass index (BMI), and genotypes as independent variables in all possible combinations. No association was observed between the apo B genotypes and serum lipids or apolipoprotein levels except for high density lipoprotein cholesterol (HDLC), apo AI and AII, with the X2 being associated with significantly lower levels of HDLC as well as apo AI and AII, the effect being stronger in males. These data raise the possibility that the mechanism of reported association between apo B polymorphism and coronary artery disease may be through effects on HDLC.     

脂蛋白脂酶基因PvuⅡ位点多态性与高脂血症人群膳食干预易感性的关系

为了解脂蛋白脂酶 (LPL)基因PvuⅡ位点多态性与高脂血症人群膳食干预效果的关系 ,从北京市西城区 8个社区居民中筛出 43 6名高脂血症患者 ,分为干预组 (2 48人 )和对照组 (188人 ) ;对两组人群进行血脂谱水平检测、膳食调查、体格检查及LPL基因PvuⅡ位点多态性检测 (PCR RFLP方法 ) ,并对干预组进行为期 6个月的膳食干预。结果表明与对照组相比 ,干预组膳食总能量、脂肪供能比及胆固醇摄入量明显降低 ,血清TC、LDL C和HDL C水平明显下降 (P <0 0 5 ) ,且LPL PvuⅡ位点 (+ +)基因型携带者TC和LDL C水平降低幅度大于 (+ - )及 (- - )基因型 ;多元线性回归分析显示膳食干预易感的因素包括LPL(+)等位基因、基限TC、LDL C水平较高以及超重等。本研究可初步得出LPL基因PvuⅡ位点 (+)等位基因与高脂血症人群膳食干预易感性密切相关 ,但限于研究对象的代表性该结论还需要进一步研究支持     

Guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI levels in chinese non-smokers

The influence of the guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein (apo) AI gene (at ?75 bp) on serum lipids and apolipoproteins was studied in 287 healthy Chinese of both sexes in Singapore. Women had significantly higher levels of high-density lipoprotein cholesterol (HDLC) and apo AI and lower low-density lipoprotein cholesterol (LDLC). The distribution of genotypes was at Hardy-Weinberg equilibrium. The frequency of the A allele in the Chinese was significantly higher [0.27; 95% confidence interval (CI) 0.24–0.31] than that reported in Caucasians (0.12; 95% CI 0.09–0.14). In men, the A allele was associated with 20% higher apo AI; this association was completely absent in women. Furthermore, in men this association was only observed in those who had never smoked, and was absent in smokers. The G/A substitution explained 9% (P < 0.02) of the sample variance of apo AI in non-smoking men. The modulating influence of smoking could not be examined in women because too few women smoke. Although the impact of this polymorphism is modulated by hormones and smoking, it is of importance in determining levels of apo AI in healthy Chinese individuals. No association of the G/A substitution of the apo AI gene was observed with any other lipid traits. © 1994 Wiley-Liss, Inc.     

Dietary exchange of an olive oil and sunflower oil blend for extra virgin olive oil decreases the estimate cardiovascular risk and LDL and apolipoprotein AII concentrations in postmenopausal women

BACKGROUND: Dietary supplementation with Virgin olive oil is considered cardioprotective. Decreasing LDL and apolipoprotein (apo) AII-lipoproteins is also appropriate for CHD protection and treatment. AIM: To study the effects of an 8%En dietary exchange of linoleic acid for oleic acid on serum and lipoprotein levels and serum and LDL-TBARS in postmenopausal women consuming a diet rich in fat (46%En; saturated/monounsaturated/polyunsaturated profile: 1.1/1.9/1). EXPERIMENTAL DESIGN: 14 postmenopausal women (63 +/- 11 years) were assigned to exchange during 28-day dietary period the culinary oil used for years consisting in a blend of olive oil plus sunflower oil (SO) for extra virgin olive oil (EVOO). SO and EVOO represented 62% of the total lipid intake. DETERMINATIONS: Dietary intakes, serum Lp(a), and cholesterol, triglycerides, phospholipids, protein, apolipoproteins AI, AII, B were determined in serum and lipoproteins. RESULTS: The dietary intervention decreased serum total cholesterol (TC), phospholipids, apo AII (all, p < 0.001) and apo B (p < 0.01). Except for triglycerides, all components of the LDL fraction decreased (at least, p < 0.05). HDL-cholesterol was not affected but HDL-phospholipids and HDL-lipids decreased (at least, p < 0.01). VLDL-apo B and VLDL-proteins decreased (all, p < 0.001). Serum Lp(a), TBARS and LDL-TBARS were not affected by the dietary exchange. The estimate of 10-year cardiovascular risk decreased (p < 0.05). Apo AII (p = 0.061) and LDL-cholesterol (p < 0.05) underwent greater modifications in normocholesterolemics, while LDL-phospholipids (p = 0.094), experienced greater alterations in hypercholesterolemics. No significant interaction was observed between dietary exchange and age (> or <65 yrs). CONCLUSIONS: These findings suggest that the dietary exchange of an olive oil and sunflower oil blend for extra virgin olive decreases LDL and apo AII levels, and the estimate of 10-year cardiovascular risk.     

Low-fat and high-monounsaturated fatty acid diets decrease plasma cholesterol ester transfer protein concentrations in young, healthy, normolipemic men

BACKGROUND: Cholesterol ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to apolipoprotein (apo) B-containing lipoproteins. The possible atherogenic role of this protein is controversial. Diet may influence plasma CETP concentrations. OBJECTIVE: The objective was to determine whether the changes in plasma lipids observed after consumption of 2 lipid-lowering diets are associated with changes in plasma CETP concentrations. DESIGN:: We studied 41 healthy, normolipidemic men over 3 consecutive 4-wk dietary periods: a saturated fatty acid-rich diet (SFA diet: 38% fat, 20% saturated fat), a National Cholesterol Education Program Step I diet (NCEP Step I diet: 28% fat, 10% saturated fat), and a monounsaturated fatty acid-rich diet (MUFA diet: 38% fat, 22% monounsaturated fat). Cholesterol content (27.5 mg/MJ) was kept constant during the 3 periods. Plasma concentrations of total, LDL, and HDL cholesterol; triacylglycerol; apo A-I and B; and CETP were measured at the end of each dietary period. RESULTS: Compared with the SFA diet, both lipid-lowering diets significantly decreased plasma total and LDL cholesterol, apo B, and CETP. Only the NCEP Step I diet lowered plasma HDL cholesterol. Positive, significant correlations were found between plasma CETP and total (r = 0.3868, P < 0.0001) and LDL (r = 0.4454, P < 0.0001) cholesterol and also between changes in CETP concentrations and those of total (r = 0.4543, P < 0.0001) and LDL (r = 0.4554, P < 0.0001) cholesterol. CONCLUSIONS: The isoenergetic substitution of a high-saturated fatty acid diet with an NCEP Step I or a high-monounsaturated fatty acid diet decreases plasma CETP concentrations.     

The effect of dietary fat on LDL size is influenced by apolipoprotein E genotype in healthy subjects

LDL particle size is dependent on both genetic factors and environmental factors such as dietary fat composition. The apolipoprotein E (apoE) genotype is a major genetic determinant of LDL size. Thus, the aim of this work was to study whether the apoE genotype interacts with the quantity and quality of dietary fat, modifying LDL size in young healthy subjects. Healthy subjects (n = 84; 66 apoE 3/3, 8 apoE 4/3, 10 apoE 3/2) were subjected to 3 dietary periods, each lasting 4 wk. The first was an SFA-enriched diet (38% fat, 20% SFA), which was followed by a carbohydrate (CHO)-rich diet (30% fat, < 10% SFA, 55% carbohydrate) or a monounsaturated fatty acid (MUFA) olive oil-rich diet (38% fat, 22% MUFA) following a randomized crossover design. At the end of each diet period, LDL particle size and plasma levels of total cholesterol, LDL cholesterol (LDL-C), HDL-C, apoB, apoA-I, and triacylglycerols were determined. LDL particle size was significantly higher (P < 0.04) in subjects with the apoE 4/3 genotype compared with those with apoE 3/3 and apoE 3/2 in the basal state. LDL size was smaller (P < 0.02) after the CHO diet than after the MUFA or SFA diets. After the CHO diet, a significant increase in LDL particle size (P < 0.035) was noted with respect to the MUFA diet in apoE 4/3 subjects, whereas a significant decrease was observed in the apoE 3/3 individuals (P < 0.043). In conclusion, a Mediterranean diet, high in MUFA-fat increases LDL particle size compared with a CHO diet, and this effect is dependent of apoE genotypes.     

Influence of apolipoprotein E genotypes on plasma lipid and lipoprotein concentrations: Results from a segregation analysis in pedigrees with molecularly defined familial hypercholesterolemia

Familial hypercholesterolemia (FH) is a monogenic disorder caused by mutations in the low-density lipoprotein (LDL) receptor gene. Large variations in plasma lipids and lipoprotein levels have been observed in FH families. These may be caused by other environmental and genetic factors of which apolipoprotein E (apo E) is a candidate. The possible influence of apo E polymorphism on components of variation in plasma LDL-C, triglycerides, high-density lipoprotein cholesterol (HDL-C), and lipoprotein(a) (Lp(a)) levels was investigated in 235 members of 14 families with FH. Sex- and age-adjusted mean LDL-C was influenced significantly by the apo E genotype in non-FH subjects (P ≤ .01), and a similar trend was observed in FH cases. Mean plasma levels of triglyceride, HDL-C, and Lp(a) were not significantly different across the apo E genotypes in FH and in non-FH family members. Complex segregation analysis was first applied to these sex- and age-adjusted data. In addition to the major gene involved in LDL-C levels (i.e., the LDL receptor gene), there was evidence for a nontransmitted environmental major factor in addition to polygenic effect that explained the mixture of distributions in TG and a major effect in addition to polygenic loci which influenced Lp(a) levels. There was no evidence for a single major factor controlling HDL-C levels in these pedigrees. When the segregation models allowed apo E regression coefficients to be ousiotype (class) specific, the results suggested that apo E genotypes have a significant effect on LDL-C, TG, and Lp(a) levels. In conclusion, the analysis presented here supports the concept that the apo E gene has an important role in the regulation of plasma lipid and lipoproteins in FH. © 1996 Wiley-Liss, Inc.     

Controlled evaluation of fat intake in the Mediterranean diet: comparative activities of olive oil and corn oil on plasma lipids and platelets in high-risk patients

Activities of low-fat diets with olive oil or corn oil on lipids and platelets were studied in 23 middle-aged patients with high atherosclerosis risk for 8 wk. The olive oil diet had a polyunsaturated-saturated ratio of 0.33 vs 1.28 for the corn oil diet. Plasma total cholesterol was reduced with corn oil, but high-density lipoprotein cholesterol levels were lower with corn oil and unchanged or raised by olive. Plasma apolipoprotein B levels were equally reduced by both diets; apolipoprotein AI and the apo AI:B ratio rose only with olive oil. Plasma-glucose levels were lowered significantly with olive oil. Changes in platelet function were characterized by a reduced sensitivity to arachidonic acid (particularly with corn oil) and to collagen (particularly with olive). An olive oil diet with a moderate fat intake (about 30% of total calories) leads to favorable plasma lipoprotein and platelet changes.     

膳食脂肪对高血压人群血脂水平的影响

目的 探讨改善膳食脂肪摄入情况对血脂的影响。方法 对营养健康教育前后高血压患者的膳食脂肪摄入情况及血脂水平进行测定分析。结果 基线调查表明人群膳食脂肪及胆固醇摄入量过高,脂肪供能比占总热能的30％以上;血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL－L）水平偏高。相关分析表明,体质指数（BMI）和饱和脂肪酸（SFA）与血清TC、TG、LDL－C呈正相关;高密度脂蛋白（HDL－C）／TC与BMI、SFA呈负相关,而与单不饱和脂肪酸（MUFA）呈正相关。进行社区营养干预后,干预组脂肪供能比小于总热能的30％,与对照组相比及自身干预前后比较差异均有显著性,胆固醇摄入量有下降趋势;干预组人群血脂TC、LDL－C水平显著降低。结论 研究结果提示减少膳食脂肪和胆固醇摄入量,适当增加单不饱和脂肪酸摄入对高血压人群降低血脂水平,控制血压是有效的。     

Effects of oleic-rich and omega-3-rich diets on serum lipid pattern and lipid oxidation in mildly hypercholesterolemic patients

AIMS: To evaluate which dietary fat elicits the best response in terms of plasma lipids, lipoproteins, and oxidative processes. METHODS: After a 4-week run-in period, 14 mildly hypercholesterolemic subjects were fed two balanced diets for 6-week periods. During the first intervention period, patients received a monounsaturated fatty acid (MUFA)-enriched diet (olive oil diet). During the second period this diet was supplemented by n-3 polyunsaturated fatty acids (PUFAs) (n-3 diet). RESULTS: After the olive oil diet, a significant decrease in total serum cholesterol (-8.54%, P<0.01), and in apolipoprotein B (Apo B) (-10.0%, P<0.01) was observed. With the addition of n-3 fatty acids no further significant changes in serum lipid concentrations were found. However, the n-3 diet was followed by an increase in lipoperoxides in isolated native low-density lipoprotein (LDL) (67.23%, P<0.01). CONCLUSIONS: A beneficial effect on the serum lipid pattern was observed with the olive oil-enriched diet. The lack of further beneficial modifications on blood lipids and lipoproteins and the increase in the oxidative susceptibility of LDL observed after the addition of n-3 PUFA to the olive oil diet does not favor the use of this diet in hypercholesterolemic patients if it is not associated with a high intake of antioxidants.     

Comparative effects of a recommended lipid-lowering diet vs a diet rich in monounsaturated fatty acids on serum lipid profiles in healthy young adults.

This crossover study investigated the effects of two fat-reduced diets, one rich in monounsaturated fatty acids (MUFAs), the other rich in polyunsaturated fatty acids (PUFAs), on serum lipid profiles in 38 healthy young adults initially on a typical western diet. After being randomly assigned to two groups, the subjects received the MUFA or PUFA diet for 3-wk and then the other diet for 3 wk. Both test diets led to significant reductions in serum cholesterol, LDL cholesterol, and HDL cholesterol (P less than 0.001). Both reduced apolipoprotein B (P less than 0.001) and apolipoprotein A-I concentrations (P less than 0.01 for the MUFA, P less than 0.001 for the PUFA diet). Apolipoprotein A-I was significantly higher on the MUFA than on the PUFA diet. The ratio of apolipoprotein A-I to B significantly increased on both diets. Thus, a low-fat, MUFA-rich diet is as effective as a low-fat, PUFA-rich diet in lowering total and LDL cholesterol, but both also lowered HDL cholesterol concentrations. The MUFA-rich diet may be more advantageous than the PUFA-rich one because it does not lower apolipoprotein A-I concentrations as much as the PUFA-rich diet.     

The peroxisome proliferator-activated receptor alpha Leu162Val polymorphism influences the metabolic response to a dietary intervention altering fatty acid proportions in healthy men

BACKGROUND: Serum lipid responses to dietary modification are partly determined by genetic factors. OBJECTIVE: We tested whether plasma lipoprotein and lipid responsiveness to a modification in the dietary ratio of polyunsaturated to saturated fatty acids (P:S) is influenced by the peroxisome proliferator-activated receptor alpha (PPARalpha) Leu162Val polymorphism in healthy men. DESIGN: Ten carriers of the V162 allele and 10 L162 homozygotes were matched according to age and body mass index (BMI). During the protocol, all subjects followed the National Cholesterol Education Program Step I diet, but intake of saturated and polyunsaturated fatty acids was adjusted to obtain a P:S of 0.3 for the first 4-wk period (low-P:S diet) and a P:S of 1.0 for the next 4-wk period (high-P:S diet). RESULTS: At screening, the PPARalpha Leu162Val polymorphism was not associated with anthropometric indexes or plasma lipoprotein and lipid concentrations. After the high-P:S diet, a significant gene-by-diet interaction was observed for changes in plasma total cholesterol, apolipoprotein (apo) A-I, and cholesterol concentrations in small LDL particles (P 相似文献   

Magnesium deficiency affects plasma lipoprotein composition in rats

Weanling rats were pair-fed for 8 d with control and Mg-deficient diets containing 960 and 30 mg of Mg/kg, respectively. The marked reduction in plasma Mg levels indicated that the rats fed the Mg-deficient diet were indeed deficient. In the Mg-deficient rats the percent composition of triglycerides in VLDL, LDL and HDL was elevated and that of protein was reduced. Although the proportion of cholesterol was reduced in LDL and HDL, that of phospholipid was decreased only in HDL. Magnesium deficiency induced a decrease in the percent composition of apolipoprotein (apo) E and a relative increase in the apo C for VLDL. In HDL from Mg-deficient rats, the proportion of apo AI was higher than normal, apo AIV was lower than normal and apo E was virtually absent. The percent composition of oleic and linoleic acids was increased but that of stearic and arachidonic acids was depressed in both VLDL and HDL derived from Mg-deficient rats compared with pair-fed controls. Whether these alterations in lipoprotein profile contribute to hyperlipoproteinemia or are the results of the metabolic changes that produce hyperlipoproteinemia remain to be determined.     

Fish consumption shifts lipoprotein subfractions to a less atherogenic pattern in humans

The effect of fish consumption on plasma lipoprotein subfraction concentrations was studied in 22 men and women (age > 40 y). Subjects were provided an average American diet (AAD, 35% of energy as fat, 14% as saturated fat, and 35 mg cholesterol/MJ) for 6 wk before being assigned to a National Cholesterol Education Program (NCEP) Step 2 high-fish diet (n = 11, 26% of energy as fat, 4.5% as saturated fat, and 15 mg cholesterol/MJ) or a NCEP Step 2 low-fish diet (n = 11, 26% of energy as fat, 4.0% as saturated fat, and 11 mg cholesterol/MJ) for 24 wk. All food and drink were provided to study participants. Consumption of the high-fish NCEP Step 2 diet was associated with a significant reduction in medium and small VLDL, compared with the AAD diet, whereas the low-fish diet did not affect VLDL subfractions. Both diets significantly reduced LDL cholesterol concentrations, without modifying LDL subfractions. Both diets also lowered HDL cholesterol concentrations. However, the high-fish diet significantly lowered only the HDL fraction containing both apolipoprotein (apo) AI and AII (LpAI:AII) and did not change HDL subfractions assessed by NMR, whereas the low-fish diet significantly lowered the HDL fraction containing only apo AI (LpAI) and the large NMR HDL fractions, resulting in a significant reduction in HDL particle size. Neither diet affected VLDL and LDL particle size. Our data indicate that within the context of a diet restricted in fat and cholesterol, a higher fish content favorably affects VLDL and HDL subspecies.     

Apolipoprotein B gene polymorphisms and serum lipids: meta-analysis of the role of genetic variation in responsiveness to diet

BACKGROUND: The genetic variance determining plasma lipid and lipoprotein concentrations may modify individual responsiveness to alterations in dietary fat and cholesterol content. OBJECTIVE: The aim was to examine the role of apolipoprotein (apo) B DNA polymorphisms in responsiveness of plasma lipids and lipoproteins to diet. DESIGN: A controlled dietary intervention study was conducted in 44 healthy, middle-aged subjects with a 3-mo baseline, a 1-mo fat-controlled, a 1-mo high-fat, and a 1-mo habitual diet period. We also conducted a meta-analysis of all published dietary trials, including our own. RESULTS: In our own dietary study, the apo B XbaI restriction-site polymorphism affected the responsiveness to diet of the plasma LDL-cholesterol concentration (P < 0.05, repeated-measures analysis of variance). Especially during the high-fat diet, homozygous absence of the XbaI restriction site (X(-)/X(-)) was associated with a greater increase in LDL cholesterol (44 +/- 5%) than was X(+)/X(+) (27 +/- 7%) or X(+)/X(-) (40 +/- 5%). The high-fat diet also induced a larger increase in plasma LDL cholesterol in subjects with the R(-)/R(-) genotype (homozygous absence of the EcoRI restriction site) (59 +/- 10%) than in those with the R(+)/R(-) (39 +/- 6%) or R(+)/R(+) (36 +/- 4%) genotype. The M(+)/M(+) genotype (homozygous presence of the MspI restriction site) was also more responsive (41 +/- 3% increase in LDL cholesterol) than the M(+)/M(-) genotype (27 +/- 10% increase). The meta-analysis supported the finding of the significant role of the EcoRI and MspI polymorphisms, but not that of the XbaI polymorphism. CONCLUSIONS: The present study indicated that the apo B EcoRI and MspI polymorphisms are associated with responsiveness to diet.