Effects of dietary fat quantity and composition on fasting and postprandial levels of coagulation factor VII and serum choline-containing phospholipids

Dietary fat influences plasma levels of coagulation factor VII (FVII) and serum phospholipids (PL). It is, however, unknown if the fat-mediated changes in FVII are linked to PL. The present study aimed to investigate the effects of dietary fat on fasting and postprandial levels of activated FVII (FVIIa), FVII coagulant activity (FVIIc), FVII protein (FVIIag) and choline-containing PL (PC). In a randomized single-blinded crossover-designed study a high-fat diet (HSAFA), a low-fat diet (LSAFA), both rich in saturated fatty acids, and a high-fat diet rich in unsaturated fatty acids (HUFA) were consumed for 3 weeks. Twenty-five healthy females, in which postprandial responses were studied in a subset of twelve, were included. The HSAFA diet resulted in higher levels of fasting FVIIa and PC compared with the LSAFA and the HUFA diets (all comparisons P< or =0.01). The fasting PC levels after the LSAFA diet were also higher than after the HUFA diet (P<0.001). Postprandial levels of FVIIa and PC were highest on the HSAFA diet and different from LSAFA and HUFA (all comparisons P< or =0.05). Postprandial FVIIa was higher on the HUFA compared with the LSAFA diet (P<0.03), whereas the HUFA diet resulted in lower postprandial levels of PC than the LSAFA diet (P<0.001). Significant correlations between fasting levels of PC and FVIIc were found on all diets, whereas FVIIag was correlated to PC on the HSAFA and HUFA diet. The present results indicate that dietary fat, both quality and quantity, influences fasting and postprandial levels of FVIIa and PC. Although significant associations between fasting FVII and PC levels were found, our results do not support the assumption that postprandial FVII activation is linked to serum PC.     

Effect of varying the ratio of n-6 to n-3 fatty acids by increasing the dietary intake of alpha-linolenic acid, eicosapentaenoic and docosahexaenoic acid, or both on fibrinogen and clotting factors VII and XII in persons aged 45-70 y: the OPTILIP study

BACKGROUND: Elevated fibrinogen, activated factor XII (FXIIa), and factor VII coagulant activity (FVIIc) are associated with higher risk of fatal ischemic heart disease. This study tested the hypothesis that lowering the dietary ratio of n-6 to n-3 polyunsaturated fatty acids (n-6:n-3) would modify these risk factors in older men and women. OBJECTIVE: The objective of the study was to measure fasting hemostatic risk factors and postprandial changes in activated FVII (FVIIa) concentrations after a 6-mo alteration in dietary n-6:n-3. DESIGN: In a randomized, parallel design in 258 subjects aged 45-70 y, we compared 4 diets providing 6% of energy as polyunsaturated fatty acids at an n-6:n-3 between 5:1 and 3:1 with a control diet that had an n-6:n-3 of 10:1. The diets were enriched in alpha-linolenic acid, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid, or both. RESULTS: Fasting and 3-h plasma triacylglycerol concentrations were 11.1% and 7.2% lower with the diet that had an n-6:n-3 of approximately 3:1 and that was enriched with EPA and DHA than with the other diets. Fasting fibrinogen, FXIIa, FVIIc, FVIIa, and FVII antigen and postprandial FVIIa were not influenced by the diets. Avoiding foods high in fat the day before measurement decreased FVIIc and FVIIa by 8% and 19.2%, respectively. A test meal containing 50 g fat resulted in a mean 47% (95% CI: 42%, 52%) increase in FVIIa 6 h later, but the response did not differ by n-6:n-3. CONCLUSION: Decreasing the n-6:n-3 to approximately 3:1 by increasing the intake of EPA and DHA lowers fasting and postprandial plasma triacylglycerol concentrations in older persons but does not influence hemostatic risk factors.     

A high fat meal activates blood coagulation factor VII in rats

In humans, high fat meals cause postprandial activation of blood coagulation factor VII (FVII), but human studies have not provided definite evidence for a prothrombotic effect of dietary FVII activation. An animal model would be an attractive way to pursue this question and therefore we tested the LEW/Mol rat. We gavaged 3 mL of a fat emulsion (n = 42) or 3 mL isotonic glucose (n = 42). Blood was sampled by heart puncture 2, 4 and 6 h (n = 14/group at each time) after the fat/glucose load. Furthermore, blood was sampled from 16 untreated rats to determine the baseline levels. Triglyceride concentrations, activated FVII (FVIIa), FVII coagulant activity (FVIIc), FVII amidolytic activity (FVIIam) and thrombin-antithrombin complexes (TAT) were determined. After fat administration, triglycerides were significantly elevated at 2 h (1.29 mmol/L) and 4 h (1.37 mmol/L) compared with baseline (0.78 mmol/L), and FVIIa was significantly raised at 4 h (54 U/L) and 6 h (58 U/L) compared with baseline (29 U/L). No postprandial changes in FVIIc, FVIIam and TAT were observed. Glucose administration did not affect any variable. We conclude that the LEW/Mol rat is a promising model for use in future studies of thrombotic effects of dietary FVII activation.     

高血压和冠心病患者组织因子途径的改变

目的 观察高血压和冠心病患者血浆组织因子（TF）、组织因子途径抑制物（TFPI）、凝血因子VII（FVII：C、FVIIa）的变化，探讨血浆TF、TFPI、FVII在组织因子途径的改变。方法 FVII：C测定采用一期凝固法，FVIIa测定采用重组可溶性组织因子法；以发色底物法测定TF、TFPI活性。观察对象包括38例高血压，40例冠心病患者以及35名健康正常人。结果 高血压和冠心病患者血浆TF与TFPI的活性高于正常对照组（P〈0．001），但TF增高程度较TFPI更为显著，故均存在TF／TFPI比值升高；且高血压、冠心病患者血浆FVII：C、FVIIa均高于正常对照组（P〈0．01），FVIIa／FVII：C比值亦增大。与高血压组相比，冠心病组TF／TFPI比值增高更为明显（P〈0．001），但FVIIa／FVII：C比值并无显著性差异（P〉0．05）。结论 高血压和冠心病患者TF／TFPI、FVIIa／FVII：C比值增高，提示存在一定的高凝倾向；并且冠心病这种倾向更为严重。     

Influence of a stearic acid-rich structured triacylglycerol on postprandial lipemia, factor VII concentrations, and fibrinolytic activity in healthy subjects

BACKGROUND: An elevated postprandial lipid concentration is believed to be atherogenic and to increase the risk of thrombosis. OBJECTIVE: The objective was to test whether the consumption of a stearic acid-rich structured triacylglycerol has adverse effects on postprandial fibrinolytic activity and lipemia, factor VII coagulant (FVII:c) activity, and activated FVII (FVIIa) concentrations. DESIGN: A randomized crossover design was used to compare the effects on middle-aged healthy men (n = 17) and women (n = 18) of meals enriched with cocoa butter, high-oleate sunflower oil (oleate), or a structured triacylglycerol containing stearic acid. RESULTS: The mean increases from fasting in plasma triacylglycerol 3 h after the oleate, cocoa butter, and structured triacylglycerol meals were 1.36 (95% CI: 1.17, 1.56), 1.39 (1.17,1.63), and 0.65 (0.50, 0.82) mmol/L, respectively. Tissue plasminogen activator activity increased and plasminogen activator type 1 activity decreased after all 3 meals. Plasma FVII:c increased after the oleate and cocoa butter meals but not after the structured triacylglycerol meal. The values 6 h after the oleate and cocoa butter meals were 11.3% (7.0%, 15.6%) and 9.9% (4.7%, 15.2%), respectively, and were significantly different (P < 0.0001 and P = 0.001, respectively) from the value after the triacylglycerol meal [2.1% (-1.1%, 5.3%)]. Plasma FVIIa increased after all 3 meals, more so after the oleate and cocoa butter meals than after the structured triacylglycerol meal. CONCLUSION: The consumption of stearic acid in the form of a structured triacylglycerol leads to less of an increase in plasma triacylglycerol and in FVII:c than does a meal enriched in cocoa butter or oleate.     

Postprandial response of activated factor VII in elderly women depends on the R353Q polymorphism.

BACKGROUND: Activated factor VII (FVIIa) is a very potent coagulant and may be a key determinant of the outcome of a cardiovascular event. The main determinants of FVIIa are the R353Q polymorphism and dietary fat intake, which may have an interactive effect. OBJECTIVE: The objective was to investigate whether the response of FVIIa to a fat-rich breakfast varies across genotypes of the R353Q polymorphism. DESIGN: Ninety-one apparently healthy elderly women (>60 y of age), 56 with the RR genotype and 35 with the RQ or QQ genotype, participated in a randomized, controlled crossover study. Subjects received 5 breakfasts, each on a separate day: 1 low-fat control breakfast and 4 high-fat test breakfasts. Blood samples were taken for measurement of FVIIa at 0800 before each breakfast (fasting) and at 1300 and 1500. RESULTS: The mean (+/-SD) fasting FVIIa concentration was 93.3 +/- 26.7 U/L in women with the RR genotype, 49.3 +/- 19.1 U/L in those with the RQ genotype and 39.5 +/- 17.2 U/L in those with the QQ genotype. The mean absolute response to all 4 test breakfasts was 37.0 U/L in those with the RR genotype and 16. 1 U/L in those carrying the Q allele (P < 0.001 for difference). Likewise, the FVIIa response relative to fasting FVIIa was significantly higher in women homozygous for the R allele. CONCLUSION: This observation may indicate a considerable difference in cardiovascular risk between genotype groups as a result of an increase in FVIIa after a fat-rich diet.     

Effect of individual dietary fatty acids on postprandial activation of blood coagulation factor VII and fibrinolysis in healthy young men

BACKGROUND: Hypertriglyceridemia may represent a procoagulant state involving disturbances to the hemostatic system. Plasminogen activator inhibitor type 1 (PAI-1) is increased in the presence of hypertriglyceridemia. Free fatty acids (FFAs) in plasma may promote factor VII (FVII) activation. OBJECTIVE: We tested the hypothesis that FVII activation would be less after consumption of saturated fatty acids than after other fatty acids. DESIGN: The effects of 6 matching dietary test fats, rich in stearic (S), palmitic (P), palmitic + myristic (M), oleic (O), trans 18:1 (T), and linoleic (L) acid, respectively, on the postprandial lipid and hemostatic profile (after 2, 4, 6, and 8 h) were investigated in 16 young men. High-fat meals (1 g fat/kg body wt; 43% from the test fatty acid) were served in the morning on 6 separate days. RESULTS: All fats increased FVII activation. The S fat resulted in a lower increase in activated FVII (FVIIa) than did the T fat and in a lower FVII coagulant activity (FVII:c) than did the O fat (P < 0.02, diet x time interaction). When the data were pooled, the saturated (S, P, and M) test fats resulted in a smaller postprandial increase in FVIIa (P = 0.036, diet effect), a smaller increase in FVII:c (P < 0.001, diet x time interaction), a greater rise in tissue plasminogen activator concentrations (P = 0.028, diet effect), and a tendency to a greater postprandial decline in PAI-1 (P = 0.06, diet effect) compared with the unsaturated test fats (O, T, and L). The increase in FVIIa was not significantly associated with the level of lipemia, plasma FFAs, or plasma lipoprotein lipase activity. CONCLUSION: Our results indicate a lesser increase in FVIIa after the consumption of saturated fats, especially the S fat, than after unsaturated test fats.     

华南汉族健康者凝血因子VII R353Q基因型的分布

目的观察凝血因子VII(coagulationf actor VII,FVII)R353Q基因多态性在华南汉族健康者人群中的分布。方法提取华南汉族60名正常健康者基因组DNA,应用多聚酶链反应(PCR)技术和限制性内切酶片段长度多态性技术检测上述人群的FVII R353Q基因型。结果华南汉族人群FVII基因R353Q具3种基因型(RR,RQ,QQ),FVII等位基因R、Q基因频率在人群中分别为90.9%,9.1%。基因型频率符合Hardy-Weinberg平衡定律。结论华南汉族健康人群凝血因子VII基因R353Q多态具3种基因型(RR,RQ,QQ),R等位基因携带频率明显高于Q等位基因。     

Are olive oil diets antithrombotic? Diets enriched with olive, rapeseed, or sunflower oil affect postprandial factor VII differently

BACKGROUND: The incidence of ischemic heart disease (IHD) in Crete was lower than expected on the basis of blood lipid concentrations of participants in the Seven Countries Study. A favorable effect of a high intake of olive oil on thrombogenesis may have contributed to this finding. OBJECTIVE: We compared the effects of virgin olive oil with those of rapeseed and sunflower oils on blood coagulation factor VII (FVII), a key factor in thrombogenesis. DESIGN: In a randomized and strictly controlled crossover study, 18 healthy young men consumed diets enriched with 5 g/MJ (19% of total energy) olive oil, sunflower oil, or rapeseed oil for periods of 3 wk. On the final day of each period, participants consumed standardized high-fat meals (42% of energy as fat). Fasting and nonfasting blood samples were collected after each period. RESULTS: Mean (+/-SEM) nonfasting peak concentrations of activated FVII (FVIIa) were 11.3 +/- 5.1 U/L lower after olive oil than after sunflower oil, an 18% reduction (P < 0.05). Olive oil also tended to cause lower FVIIa peak concentrations than did rapeseed oil (mean difference: 8.6 U/L, a 15% reduction; P = 0.09). There were no significant differences between diets with respect to nonfasting factor VII coagulant activity (FVII:c), prothrombin fragment 1+2 (F1+2), and tissue factor pathway inhibitor (TFPI) concentrations, or with respect to fasting plasma values of FVII protein, FVII:c, FVIIa, F1+2, or TFPI. CONCLUSION: A background diet rich in olive oil may attenuate the acute procoagulant effects of fatty meals, which might contribute to the low incidence of IHD in Mediterranean areas.     

Effects of the FABP2 A54T mutation on triglyceride metabolism of viscerally obese men.

OBJECTIVE: Viscerally obese individuals are frequently characterized by a proatherogenic condition. A missense mutation (A54T) in the fatty acid binding protein type 2 (FABP2) gene has been associated with insulin resistance and obesity. This study examined the effect of this mutation on lipoprotein levels in viscerally obese hyperinsulinemic condition. RESEARCH METHODS AND PROCEDURES: A total of 217 men were assigned to one of two groups based on their FABP2 A54T polymorphism. RESULTS: The two genotypic groups showed no difference in either physiological characteristics or lipoprotein/lipid profile, before or after statistical adjustment for age. From this initial sample, 50 men accepted to have their postprandial lipid response assessed and 10 T54/A54 heterozygotes were then individually matched for visceral adipose tissue accumulation and fasting plasma triglyceride (TG) levels with 10 A54/A54 homozygotes. High-density lipoprotein (HDL)-TG levels were significantly increased in the fasting state as well as 4 hours after the test meal (p = 0.04 and p = 0.0008, respectively) in men bearing the A54T mutation. In addition, the area under the curve of postprandial HDL-TG levels was also significantly higher among T54/A54 heterozygotes than among A54/A54 homozygotes (p = 0.04). Interestingly, fasting TG concentrations in large TG-rich lipoproteins (large-TRL; S(f) > 400) were correlated with HDL-TG levels at 4 (r = 0.74, p = 0.01) and 8 hours (r = 0.73, p = 0.01) after the test meal in T54/A54 heterozygotes only. DISCUSSION: The FABP2 A54T missense mutation may contribute to the TG enrichment of HDL in the postprandial state that, in turn, may alter the risk of atherosclerotic vascular disease.     

The solid fat content of stearic acid-rich fats determines their postprandial effects

BACKGROUND: The process of randomization is used commercially to harden fats as an alternative to partial hydrogenation, but its effects on cardiovascular disease risk factors are uncertain. OBJECTIVE: The objective was to compare the chronic and acute effects of randomization of a fat rich in 1,3-distearyl, 2-oleyl glycerol on fasting and postprandial lipids, glucose, insulin, and activated clotting factor VII (FVIIa) concentrations. DESIGN: A crossover design study in 16 men compared fasting and postprandial lipid, glucose, insulin, and FVIIa concentrations at baseline and after a 3-wk diet providing 30 g unrandomized or randomized shea butter and sunflower oil blends (SSOBs), both of which contained approximately 50% stearic acid. Fecal fat excretion was measured during each dietary period. Postprandial changes were assessed after the consumption of meals providing 50 g test fat. A subsequent study compared postprandial changes after the consumption of an oleic acid-rich sunflower oil meal and an unrandomized SSOB meal. RESULTS: Both SSOBs were well digested and absorbed. Randomization did not affect fasting or postprandial lipid, glucose, insulin, or FVIIa concentrations. Compared with the oleic acid-rich meal, the unrandomized SSOB resulted in 53% lower postprandial lipemia, 23% higher hepatic lipase activity, and a 25% lower postprandial increase in FVIIa concentration. The solid fat contents at 37 degrees C were 22%, 41%, and 0% with the unrandomized SSOB, randomized SSOB, and oleic acid-rich meals, respectively. CONCLUSIONS: Stearic acid-rich triacylglycerol in both unrandomized and randomized forms does not adversely affect lipid risk factors for cardiovascular disease. The high proportion of solid fat at 37 degrees C may explain the decreased postprandial lipemic response.     

Effect of modified dairy fat on fasting and postprandial haemostatic variables in healthy young men

It has been suggested that milk fat, due to its content of saturated fatty acids, may have a thrombogenic effect. In the present study the fatty acid profile of milk fat was modified by changing the feeding regimens of cows and the effect on haemostatic variables of a diet containing the modified milk fat (M) was compared with that of a diet containing milk fat of typical Danish composition (D). In the modified fat 16% of the saturated fatty acid (C12-C16) content was replaced mainly by oleic acid. Eighteen subjects were fed on two strictly controlled isoenergetic diets containing 40% energy from total fat (30% energy from the test fats) for periods of 4 weeks in a study with a crossover design. Fasting samples were taken in the last week of each study period. Postprandial samples were taken on day 21, 3 h after lunch (n 18), and on the last day of the study 2, 4, 6 and 8 h after a fat load containing 1.2 g of one of the milk fats/kg body weight (n 8). After 4 weeks' dietary intervention fasting plasma factor VII coagulant (FVIIc) activity, tissue-type plasminogen activator (t-PA) activity, plasminogen activator inhibitor (PAI-1) antigen and beta-thromboglobulin did not differ between diets M and D. Postprandially FVIIc and t-PA activities increased (P < 0.001) and PAI-1 antigen and PAI-1 activity decreased (P < 0.001) as compared with fasting values, regardless of diet. After the fat load, the postprandial increase in FVIIc was marginally lower after diet M than diet D (diet effect, P < 0.05). In conclusion, the modified milk fat obtained by the applied feeding strategy had virtually the same effects on haemostatic variables as conventional milk fat.     

Dietary monounsaturated fatty acids and haemostasis.

Diets high in monounsaturated fatty acids (MUFA) are increasingly being recommended as a highly-effective cholesterol-lowering strategy in populations at risk of CHD. However, the need for a re-appraisal of the benefits of diets rich in MUFA became apparent as a result of recent studies showing that meals high in olive oil cause greater postprandial activation of blood coagulation factor VII than meals rich in saturated fatty acids. The present review evaluates the evidence for the effects of MUFA-rich diets on fasting and postprandial measurements of haemostasis, and describes data from a recently-completed long-term controlled dietary intervention study. The data show that a background diet high in MUFA has no adverse effect on fasting haemostatic variables and decreases the postprandial activation of factor VII in response to a standard fat-containing meal. Since the same study also showed a significant reduction in the ex vivo activation of platelets in subjects on the high-MUFA diet, the overall findings suggest that there is no reason for concern regarding adverse haemostatic consequences of high-MUFA diets.     

Influence of triacylglycerol structure on the postprandial response of factor VII to stearic acid-rich fats

BACKGROUND: The consumption of a synthetic, randomized, stearic acid-rich triacylglycerol results in decreased postprandial lipemia and activated factor VII (FVII:a) compared with cocoa butter (a nonrandomized, symmetrical, stearic acid-rich triacylglycerol). It was hypothesized that this difference is a consequence of the differences in structure between the 2 triacylglycerols. OBJECTIVE: The objective was to test whether the consumption of randomized cocoa butter decreases postprandial lipemia and FVII:a. DESIGN: A randomized crossover trial with 17 male subjects compared the effects of meals containing 50 g fat provided as a symmetrical (cocoa butter) or an asymmetrical (randomized cocoa butter) triacylglycerol on postprandial changes in lipids, chylomicron composition, and FVII:a. RESULTS: After randomization, the postprandial area under the curve for plasma triacylglycerol decreased by 41% (P < 0.01). At 3 h the plasma concentrations of triacylglycerol, palmitic acid, stearic acid, and oleic acid were 26%, 18%, 34%, and 19% lower, respectively. The proportion of oleic acid in the sn-2 position of the chylomicron triacylglycerol was reduced from 67.4 mol% to 35.9 mol% and resulted in an increase in the proportion of stearic acid in the sn-2 position from 9.2 mol% to 25.4 mol%. FVII:a did not increase 6 h after consumption of the randomized cocoa butter (: 1.2; 95% CI: -2.7, 4.6 U/L) but increased significantly (: 7.7; 95% CI: 2.5,12.9 U/L) 6 h after consumption of the unrandomized cocoa butter. CONCLUSIONS: Symmetrical stearic acid-rich triacylglycerol with oleic acid in the sn-2 position appears to be absorbed more rapidly than is asymmetrical triacylglycerols with long-chain saturated fatty acids in the sn-2 position, which leads to activation of FVII.     

老年冠心病患者餐后血脂变化及其对血小板活性的影响

目的　探讨老年冠心病 (CHD)患者餐后血脂代谢特点以及对血小板活性的影响。方法　对 48例老年冠心病 (CHD)患者 (冠心病组 )和 3 0例老年健康自愿者 (对照组 )均禁食 12h后 ,分别接受脂肪餐负荷试验 ,于空腹及餐后 4h测定血清甘油三酯(TG)、总胆固醇 (CH)、高密度脂蛋白 (HDL -C)、低密度脂蛋白 (LDL -C)水平 ,并同时于空腹状态及餐后 4h采用生物活性法测定血小板衍生生长因子 (PDGF)、用酶联免疫标测法 (ELISA)检测血管性假血友病因子 (vWF)浓度。结果　冠心病组餐前及餐后 4hTG(P<0 0 1)、CH(P <0 0 5 )、LDL -C(P <0 0 1)、PDGF(P <0 0 1)、vWF(P <0 0 1)值均显著高于对照组 ,HDL -C(P <0 0 1)显著低于对照组。餐后 4h与餐前比较 ,TG、CH、LDL -C值明显上升 ,而HDL -C下降幅度无明显差异。冠心病组PDGF、vWF值在餐后 4h上升幅度存在显著性差异 (P <0 0 5 )。结论　老年冠心病人存在血脂代谢异常。餐后血脂更能反映老年人的代谢水平。餐后血脂代谢异常对血小板活化起促进作用 ,血小板反复活化可能参与了冠状动脉硬化早期病变     

FABP2 Ala54Thr genotype is associated with glucoregulatory function and lipid oxidation after a high-fat meal in sedentary nondiabetic men and women

BACKGROUND: A common functional missense mutation [Ala54Thr of the fatty acid-binding protein 2 gene (FABP2)] has previously been studied for associations with glucoregulation, postprandial lipemia, and lipid oxidation rates. However, most of those studies have not accounted for the interactive and potentially confounding effects of habitual physical activity and diet. OBJECTIVE: We tested the hypothesis that, in sedentary nondiabetic subjects following a low-fat diet, Thr54 FABP2 carriers have lower glucoregulatory function, greater postprandial lipemia, and greater lipid oxidation rates than do their Ala54 FABP2-homozygous counterparts. DESIGN: Men and women (n = 122) aged 50-75 y who were following a low-fat diet were genotyped and underwent oral-glucose-tolerance tests. A subgroup (n = 36) also underwent postprandial lipemia tests with lipid oxidation rate measurements. RESULTS: Thr54 carriers were less likely to have normal glucose tolerance (P = 0.05) and had higher fasting glucose concentrations (P = 0.003) than did Ala54 homozygotes. In Thr54 carriers, the insulin sensitivity index was lower (P = 0.02), and the fasting insulin and the oral-glucose-tolerance test insulin area under the curve were higher (P = 0.05 and 0.03, respectively) than in Ala54 homozygotes. FABP2 genotype was not associated with fasting or postprandial lipemia test triacylglycerol or free fatty acids (P > or = 0.22 for all), but postprandial lipid oxidation rates were higher (P = 0.01), which suggests that fat absorption is higher in Thr54 carriers than in Ala54 homozygotes. CONCLUSIONS: In sedentary nondiabetic persons following a low-fat diet, FABP2 Thr54 carriers have lower glucose tolerance and lower insulin action than do Ala54-homozygous persons. Furthermore, FABP Thr54 carriers have higher lipid oxidation rates, which may be the mechanism of glucoregulatory dysfunction.     

CBS基因变异与血清同型半胱氨酸水平及先天性心脏病的关系研究

目的探讨核心家庭胱硫脒β-合酶(CBS)基因变异与子代发生先天性心脏病(CHDs)的关系。方法选择辽宁省234名CHDs患者(男116人,女118人)及其生物学父母作为病例组;选取同地区无出生缺陷病史及家族史的136名正常人(男78人,女58人)及其生物学父母作为对照组。所有研究对象均采集血样,提取血凝块DNA,分别以PCR和PCR-ARMS方法检测CBS基因844ins68和G919A位点基因型;对部分家庭的母亲和子代以荧光免疫偏振法检测血清tHcy水平。结果各组人群CBS基因844ins68和G919A位点基因型分布已达到Hardy-Weinberg遗传平衡。CBS 844ins68位点分析表明,与纯合野生型(DD)相比,母亲、父亲、子代杂合子(DI)的比值比[ORs(95%CI)]值分别为14.19(2.21,591.52)、4.37(1.24,23.47)和4.77(1.38,25.37)。CBS基因G919A位点分析表明,与GG基因型相比,杂合子GA和纯合子AA的ORs(95%CI)值分别为0.45(0.23,0.87)和0.34(0.11,1.01);母亲GA、父亲GA和AA基因型携带者其子代罹患先心病的危险性均明显降低,ORs(95%CI)值分别为0.44(0.23,0.84)、0.54(0.29,1.00)和0.24(0.08,0.71)。基因型联合分析表明,与无危险等位基因的基因型组合(0组)相比,母亲、父亲、子代携带2个危险等位基因者(组2)的ORs(95%CI)值分别为4.32(1.07,20.66)、3.43(0.88,13.71)和8.62(1.69,82.72),且均有统计学意义。不同组别血清tHcy水平比较表明,病理组与对照组tHcy水平无明显差异,CBS不同基因型间tHcy水平差异亦无显著性(P>0.05)。结论CBS基因844ins68位点杂合子(DI)以及G919A位点突变等位基因(A)与先心病高危险性有关,但对血清tHcy水平无明显影响。     

Effect of ferroportin Q248H polymorphism on iron status in African children

BACKGROUND: Iron deficiency is common in African children, but genetic variations affecting susceptibility have not been identified. The Q248H mutation in ferroportin, a cellular iron exporter regulated by iron status and inflammation, may be associated with high iron stores in African adults. OBJECTIVE: The study examined the prevalence of iron deficiency in African children in an area where malaria transmission is low to absent and investigated whether ferroportin Q248H provides protection from iron deficiency. DESIGN: Complete blood counts, serum markers of iron status and inflammation, and ferroportin Q247H were measured in 208 preschool children in Harare, Zimbabwe. Iron deficiency was defined by serum ferritin and C-reactive protein (CRP) concentrations (definition 1) or by ferritin and the ratio of transferrin receptor to log10 ferritin (definition 2). RESULTS: Q248H was present in 40 children (38 heterozygotes, 2 homozygotes), elevated CRP was present in 26 (12.5%), and iron deficiency was present in 50 (24.0%) (definition 1) or 55 (26.4%) (definition 2). The interaction between ferroportin Q248H and CRP was significant for ferritin concentrations (P = 0.027) in a 2-factor analysis of variance model. With elevated CRP, the estimated geometric mean (SE range) ferritin concentration was 74 (52-106) microg/L for Q248H heterozygotes but 24 (20-30) microg/L for wild-type subjects (P = 0.016). With normal CRP, the ferritin concentration was 16 (14-19) microg/L whether or not the mutation was present. After adjustment for age and weight-for-height z score, the odds ratio (OR) for iron deficiency in Q248H heterozygotes was not significant according to definition 1 (OR: 0.53; 95% CI: 0.18, 1.40; P = 0.222) or definition 2 (OR: 0.39; 95% CI: 0.14, 1.07; P = 0.068). CONCLUSIONS: Any effect of Q248H in protecting against iron deficiency may be observable in children exposed to repeated inflammatory conditions. Further studies of iron status and ferroportin Q248H in African children are needed.     

Postprandial responses of individual fatty acids in subjects homozygous for the threonine- or alanine-encoding allele in codon 54 of the intestinal fatty acid binding protein 2 gene

BACKGROUND: The affinity of intestinal fatty acid binding protein (FABP) for fatty acids is regulated by the polymorphism at codon 54 of the FABP2 gene (alanine-to-threonine shift). We found earlier that the threonine-encoding allele (Thr54) is associated with an increased postprandial lipemic response. OBJECTIVE: We studied the postprandial responses of individual fatty acids in subjects homozygous for the Thr54 or alanine-encoding allele (Ala54). DESIGN: Oral-fat-loading tests were performed in 8 subjects homozygous for Thr54 and in 7 subjects homozygous for Ala54. RESULTS: The postprandial responses of most of the 14-18-carbon fatty acids in chylomicron and VLDL triacylglycerols were significantly elevated in the Thr54 homozygotes whereas the relative increases in these fatty acids were not significantly different in both groups. The amounts of 20- and 22-carbon polyunsaturated fatty acids started to increase later than the amounts of shorter ones after the test meal, and the differences between the groups were mostly insignificant. The responses of chylomicron fatty acids correlated positively with postprandial insulin response in the Thr54 homozygotes and inversely in the Ala54 homozygotes. VLDL fatty acid responses correlated with fasting triacylglycerol concentrations in the Ala54 homozygotes but not in the Thr54 homozygotes. CONCLUSION: The threonine-encoding allele of the FABP2 gene is associated with an increased postprandial response of 14-18-carbon fatty acids but not with changes in the relative amounts of individual fatty acids introduced to chylomicron triacylglycerols.     

Postprandial hyperglycemia and insulin sensitivity differ among lean young adults of different ethnicities

Both postprandial hyperglycemia and insulin resistance (IR) have implications for the development of cardiovascular disease. The present study was designed to examine differences in postprandial glycemia and insulin sensitivity among young adults of different ethnic origins. Lean, healthy subjects (n = 60) from five ethnic groups [20 European Caucasians, 10 Chinese, 10 South East (SE) Asians, 10 Asian Indians and 10 Arabic Caucasians] were matched for age, body mass index, waist circumference, birth weight and current diet. A 75-g white bread carbohydrate challenge was fed to assess postprandial glycemia and insulinemia. Insulin sensitivity was assessed in three groups by the euglycemic-hyperinsulinemic clamp and in all subjects by homeostasis model assessment (HOMA) modeling. Postprandial hyperglycemia (incremental area under the curve) and insulin sensitivity (M-value) both showed a twofold variation among the groups (P < 0.001) and were significantly related to each other (R(2) = 56%, P < 0.001). Young SE Asians had the highest postprandial glycemia and lowest insulin sensitivity, whereas European and Arabic Caucasian subjects were the most insulin sensitive and carbohydrate tolerant. These findings suggest that IR is evident even in lean, young adults of some ethnic groups and is associated with significant increases in postprandial glycemia and insulinemia in response to a realistic carbohydrate load.