老年人小肠脂肪酸结合蛋白基因54位密码子多态性与血脂水平的关系

目的 调查老年人小肠脂肪酸结合蛋白(I-FABP)基因外显子2中54位点密码子A/T 单核苷酸多态性和不同基因型人群的血脂水平,探讨I-FABP基因多态性与老年人血脂水平的关系.方法 采用聚合酶链反应(PCR)、DNA限制性内切酶酶切等技术对72例汉族老年人54A/T I-FABP基因型进行分析;用全自动生化仪检测入选人群的血浆总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)水平.结果 基因型分组Thr54(-)组、Thr54(+)组各36例,Thr54(-)组与Thr54(+)组比较,TC为(4.50±0.73) mmol/L与(5.48±0.49)mmol/L、TG为(1.08±0.48)mmol/L与(2.02±0.53) mmol/L、LDL-C为(3.10±0.44)mmol/L与(3.50±0.66) mmol/L和HDL-C为(1.14±0.25)mmol/L与(0.96±0.23) mmol/L,差异有统计学意义(t值分别为-6.67、-7.84、-3.03、3.05,均P＜0.05).结论 I-FAB外显子2中54位点密码子A/T SNP与老年人群的血脂水平相关.     

The association of fatty acid-binding protein 2 A54T polymorphism with postprandial lipemia depends on promoter variability

Studies on the association of fatty acid-binding protein 2 (FABP2) A54T and promoter polymorphism, and type 2 diabetes mellitus, insulin, and triglyceride levels are controversial. The aim of this study was to investigate the interfering effect of FABP2 A54T and promoter polymorphism on the postprandial response to a mixed meal and an oral glucose load. Seven hundred men from the Metabolic Intervention Cohort Kiel underwent a standard glucose tolerance test and a standardized mixed meal test and were genotyped by use of the Taqman method. When calculated independently from promoter variability, postprandial triglyceride levels were significantly higher and postprandial insulin sensitivity (homeostasis model assessment index) was lower in homozygous carriers of FABP2 T54T compared with carriers of the FABP2 exon wild-type allele (FABP2 A54A and A54T). This confirms previous findings. The effect of the exon T54T genotype on triglyceride levels and insulin sensitivity, however, was dependent on promoter variability. We found a significant increase in postprandial triglyceride levels and a decrease in insulin sensitivity due to T54T only in the presence of the homozygous B genotype at the promoter polymorphism. Similar results were obtained after oral glucose tolerance test. Reporter gene assays indicated a higher responsiveness to peroxisome proliferator-activating receptor-γ (PPAR-γ)/retinoid X receptor (RXR) of FABP2 promoter B vs promoter A. Synergism between a higher inducibility of FABP2 expression and a higher activity of T54 variant may explain higher postprandial triglycerides in case of combined genotype (promoter B + T54). This interference and different linkage disequilibrium between FABP2 exon and promoter polymorphisms may explain the different results obtained in different cohorts.     

脂肪细胞型脂肪酸结合蛋白与代谢综合征

脂肪细胞型脂肪酸结合蛋白(A-FABP)是近年来新发现的脂肪因子.动物实验表明其可以促进代谢综合征各组分如胰岛素抵抗、血脂紊乱、2型糖尿病和动脉粥样硬化的发生、发展.人群研究也发现,其过度表达而导致血浆中含量增加是反映代谢综合征的一个可靠生物标志物.随着研究的深入,A-FABP对于治疗代谢综合征的作用也日益受到人们的关注.以下主要就近年来有关A-FABP的分布、结构、特性及其与代谢综合征组分的关系作一综述.     

Codon-54 polymorphism of the fatty acid-binding protein 2 gene is associated with elevation of fasting and postprandial triglyceride in type 2 diabetes

Patients with type 2 diabetes are frequently dyslipidemic or hypertriglyceridemic. To assess whether increased intestinal triglyceride input leads to elevated fasting and postprandial triglycerides in type 2 diabetes, we used the codon 54 polymorphism of the fatty acid-binding protein 2 gene, which results in the substitution of threonine (Thr) for alanine and is associated with increased intestinal input of triglyceride. Of the 287 diabetic patients screened, 108 (37.6%) were heterozygous and 31 (10.8%) were homozygous for the Thr-54 allele. Mean (+/-SEM) fasting plasma triglyceride levels in patients with the wild-type (n = 80), those heterozygous for the Thr-54 allele (n = 57), and those homozygous for it (n = 18) were 2.0 +/- 0.09, 2.7 +/- 0.20, and 3.8 +/- 0.43 mmol/L, respectively. A linear relationship of mean fasting plasma triglyceride levels (r2 = 0.97) between the 3 groups was found. After fat ingestion, the postprandial area under the curve of plasma triglyceride (P = 0.025) and chylomicrons (Sf > 400, P = 0.013) was higher in the Thr-54/Thr-54 (n = 6) than in the wild-type (n = 9). Our results are consistent with the hypothesis that, in type 2 diabetes, increased intestinal input of triglyceride can lead to elevated fasting and postprandial plasma triglycerides.     

Meta-analysis on the effect of the Ala54Thr polymorphism of the fatty acid-binding protein 2 gene on body mass index

Background and aim

The results from studies published on the association of fatty acid-binding protein 2 (FABP2) Ala54Thr polymorphism with body mass index (BMI) are conflicting. In this meta-analysis, we investigated the association of the FABP2 Ala54Thr polymorphism with BMI.

Methods and results

We searched for articles published prior to June 2009 using PubMed, HugeNavigator and China National Knowledge Internet. The languages were limited to English and Chinese. Data on BMI were collected. A pooled weighted mean difference (WMD), together with 95% confidence interval (CI), was used for this meta-analysis.A total of 27 studies with 10 974 subjects were included in this meta-analysis. The pooled effect for dominant, recessive and co-dominant model comparisons did not suggest the significant association between the FABP2 Ala54Thr polymorphism and BMI in overall populations: WMD_{fixed effects} = −0.00, 95% CI: (−0.16 to 0.15), p = 0.99, WMD_{random effects} = −0.00, 95% CI: (−0.16 to 0.15), p = 0.99, p_Q = 0.77, I² = 0%, WMD_{fixed effects} = −0.12, 95% CI: (−0.39 to 0.14), p = 0.35, WMD_{random effects} = −0.12, 95% CI: (−0.39 to 0.14), p = 0.35, p_Q = 0.47, I² = 0% and WMD_{fixed effects} = 0.07, 95% CI: (−0.11 to 0.25), p = 0.45, WMD_{random effects} = 0.07, 95% CI: (−0.11 to 0.25), p = 0.45, p_Q = 0.90, I² = 0%, respectively. The results from the comparisons of ThrThr versus AlaAla and AlaThr versus AlaAla showed no evidence that the FABP2 Ala54Thr polymorphism is significantly associated with BMI in overall populations (p > 0.05). All the results from the subgroup analyses for these genetic models comparisons were not significant (p > 0.05).

Conclusions

Our meta-analysis does not support the association between the FABP2 Ala54Thr polymorphism and BMI.     

Association of the intestinal fatty acid-binding protein Ala54Thr polymorphism and abdominal adipose tissue in African-American and Caucasian women

Genetic variants in the intestinal fatty acid-binding protein-2 (FABP2) gene have been associated with body composition phenotypes. We examined the association between the Ala(54)Thr variant in the FABP2 gene and levels of visceral (VAT) and sc (SAAT) abdominal fat in a group of 223 premenopausal African-American (n = 103) and Caucasian (n = 120) women. Subjects were genotyped for the marker. In addition, body composition was assessed by dual energy x-ray absorptiometry, and VAT was determined from a single computed tomography scan. The frequency of the Thr mutant allele did not differ significantly by ethnic group. After adjusting for total body fat, total abdominal adipose tissue (TAT) and SAAT were significantly lower in carriers of either one or two copies of the mutant Thr allele (P < 0.01). There was no association between total fat mass or VAT and the FABP2 polymorphism. Separate analyses by ethnic group showed that the association between the polymorphism and TAT and SAAT was observed in Caucasian (P < 0.01), but not in African-American (not significant), women. We conclude that women carriers of the FABP2 Thr allele have lower TAT and SAAT than noncarriers of the mutation. This association is present in Caucasian, but not in African-American, women.     

Adipocyte fatty acid-binding protein in obese children before and after weight loss

Adipocyte fatty acid-binding protein (A-FABP) has been reported to be increased in obese adults and to be related to metabolic syndrome. Because studies concerning A-FABP in weight loss are limited and studies in obese children are missing, we analyzed A-FABP in obese children before and after weight loss. Fasting serum A-FABP, leptin, insulin, glucose, triglycerides, low-and high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and tumor necrosis factor alpha concentrations as markers of the metabolic syndrome, and weight status (body mass index and percentage body fat based on skinfold measurements) were determined in 30 obese children (median age, 11.9 years) before and after participating in a 1-year obesity intervention. Furthermore, A-FABP levels were measured in 10 nonobese children of similar age, sex, and pubertal stage. Obese children had significantly (P < .001) higher A-FABP concentrations compared with nonobese children. In backward multivariate linear regression analysis, A-FABP correlated significantly (P < .05) with percentage body fat and leptin, but not with any of the markers of the metabolic syndrome. Changes of A-FABP concentrations correlated significantly with changes of percentage body fat (r = 0.53, P = .001) and leptin (r = 0.55, P < .001), but not with any changes of parameters of the metabolic syndrome. Substantial weight loss in 10 children led to a significant (P < .05) decrease in A-FABP levels in contrast to the 20 children without change of weight status. In cross-sectional as well as longitudinal analyses, A-FABP levels were related to weight status and leptin levels. Further longitudinal studies are necessary to study the relationship between A-FABP concentrations and parameters of the metabolic syndrome.     

脂肪细胞型脂肪酸结合蛋白与代谢综合征相关

Serum adipocyte fatty acid-binding protein (A-FABP) was raised in metabolic syndrome (MS)patients (n= 121) as compared with age-matched healthy subjects [n = 120, (14.7±4.8 vs 6.8 ±3. 0) μg/L,P<0.001]. It reached higher level in MS subjects with visceral obesity [(15.7±4.2 vs 12.6±5.1) μg/L, P<0.001]. Serum A-FABP concentration was positively correlated with body mass index, waist circumference, waist-tohip ratio, fasting insulin, homeostasis assessment for insulin resistance (HOMA-IR), fasting glucose, triglycerides,total cholesterol,and mean arterial blood pressure, whereas negatively correlated with HDL-C (r =-0. 448, P< 0.001).     

脂肪细胞型脂肪酸结合蛋白与代谢综合征相关

Serum adipocyte fatty acid-binding protein (A-FABP) was raised in metabolic syndrome (MS)patients (n= 121) as compared with age-matched healthy subjects [n = 120, (14.7±4.8 vs 6.8 ±3. 0) μg/L,P<0.001]. It reached higher level in MS subjects with visceral obesity [(15.7±4.2 vs 12.6±5.1) μg/L, P<0.001]. Serum A-FABP concentration was positively correlated with body mass index, waist circumference, waist-tohip ratio, fasting insulin, homeostasis assessment for insulin resistance (HOMA-IR), fasting glucose, triglycerides,total cholesterol,and mean arterial blood pressure, whereas negatively correlated with HDL-C (r =-0. 448, P< 0.001).     

脂肪细胞型脂肪酸结合蛋白与代谢综合征相关

Serum adipocyte fatty acid-binding protein (A-FABP) was raised in metabolic syndrome (MS)patients (n= 121) as compared with age-matched healthy subjects [n = 120, (14.7±4.8 vs 6.8 ±3. 0) μg/L,P<0.001]. It reached higher level in MS subjects with visceral obesity [(15.7±4.2 vs 12.6±5.1) μg/L, P<0.001]. Serum A-FABP concentration was positively correlated with body mass index, waist circumference, waist-tohip ratio, fasting insulin, homeostasis assessment for insulin resistance (HOMA-IR), fasting glucose, triglycerides,total cholesterol,and mean arterial blood pressure, whereas negatively correlated with HDL-C (r =-0. 448, P< 0.001).     

脂肪细胞型脂肪酸结合蛋白与代谢综合征相关

Serum adipocyte fatty acid-binding protein (A-FABP) was raised in metabolic syndrome (MS)patients (n= 121) as compared with age-matched healthy subjects [n = 120, (14.7±4.8 vs 6.8 ±3. 0) μg/L,P<0.001]. It reached higher level in MS subjects with visceral obesity [(15.7±4.2 vs 12.6±5.1) μg/L, P<0.001]. Serum A-FABP concentration was positively correlated with body mass index, waist circumference, waist-tohip ratio, fasting insulin, homeostasis assessment for insulin resistance (HOMA-IR), fasting glucose, triglycerides,total cholesterol,and mean arterial blood pressure, whereas negatively correlated with HDL-C (r =-0. 448, P< 0.001).     

脂肪细胞型脂肪酸结合蛋白与代谢综合征相关

Serum adipocyte fatty acid-binding protein (A-FABP) was raised in metabolic syndrome (MS)patients (n= 121) as compared with age-matched healthy subjects [n = 120, (14.7±4.8 vs 6.8 ±3. 0) μg/L,P<0.001]. It reached higher level in MS subjects with visceral obesity [(15.7±4.2 vs 12.6±5.1) μg/L, P<0.001]. Serum A-FABP concentration was positively correlated with body mass index, waist circumference, waist-tohip ratio, fasting insulin, homeostasis assessment for insulin resistance (HOMA-IR), fasting glucose, triglycerides,total cholesterol,and mean arterial blood pressure, whereas negatively correlated with HDL-C (r =-0. 448, P< 0.001).     

脂肪细胞型脂肪酸结合蛋白与代谢综合征相关

Serum adipocyte fatty acid-binding protein (A-FABP) was raised in metabolic syndrome (MS)patients (n= 121) as compared with age-matched healthy subjects [n = 120, (14.7±4.8 vs 6.8 ±3. 0) μg/L,P<0.001]. It reached higher level in MS subjects with visceral obesity [(15.7±4.2 vs 12.6±5.1) μg/L, P<0.001]. Serum A-FABP concentration was positively correlated with body mass index, waist circumference, waist-tohip ratio, fasting insulin, homeostasis assessment for insulin resistance (HOMA-IR), fasting glucose, triglycerides,total cholesterol,and mean arterial blood pressure, whereas negatively correlated with HDL-C (r =-0. 448, P< 0.001).     

脂肪细胞型脂肪酸结合蛋白与代谢综合征相关

Serum adipocyte fatty acid-binding protein (A-FABP) was raised in metabolic syndrome (MS)patients (n= 121) as compared with age-matched healthy subjects [n = 120, (14.7±4.8 vs 6.8 ±3. 0) μg/L,P<0.001]. It reached higher level in MS subjects with visceral obesity [(15.7±4.2 vs 12.6±5.1) μg/L, P<0.001]. Serum A-FABP concentration was positively correlated with body mass index, waist circumference, waist-tohip ratio, fasting insulin, homeostasis assessment for insulin resistance (HOMA-IR), fasting glucose, triglycerides,total cholesterol,and mean arterial blood pressure, whereas negatively correlated with HDL-C (r =-0. 448, P< 0.001).     

脂肪细胞型脂肪酸结合蛋白与代谢综合征相关

Serum adipocyte fatty acid-binding protein (A-FABP) was raised in metabolic syndrome (MS)patients (n= 121) as compared with age-matched healthy subjects [n = 120, (14.7±4.8 vs 6.8 ±3. 0) μg/L,P<0.001]. It reached higher level in MS subjects with visceral obesity [(15.7±4.2 vs 12.6±5.1) μg/L, P<0.001]. Serum A-FABP concentration was positively correlated with body mass index, waist circumference, waist-tohip ratio, fasting insulin, homeostasis assessment for insulin resistance (HOMA-IR), fasting glucose, triglycerides,total cholesterol,and mean arterial blood pressure, whereas negatively correlated with HDL-C (r =-0. 448, P< 0.001).     

脂肪细胞型脂肪酸结合蛋白与代谢综合征相关

Serum adipocyte fatty acid-binding protein (A-FABP) was raised in metabolic syndrome (MS)patients (n= 121) as compared with age-matched healthy subjects [n = 120, (14.7±4.8 vs 6.8 ±3. 0) μg/L,P<0.001]. It reached higher level in MS subjects with visceral obesity [(15.7±4.2 vs 12.6±5.1) μg/L, P<0.001]. Serum A-FABP concentration was positively correlated with body mass index, waist circumference, waist-tohip ratio, fasting insulin, homeostasis assessment for insulin resistance (HOMA-IR), fasting glucose, triglycerides,total cholesterol,and mean arterial blood pressure, whereas negatively correlated with HDL-C (r =-0. 448, P< 0.001).     

脂肪细胞型脂肪酸结合蛋白与代谢综合征相关

代谢综合征(MS)组(n=121)的血清脂肪细胞型脂肪酸结合蛋白(A-FABP)水平较对照组(n=120)显著升高[(14.7±4.8 vs 6.8±3.0)μg/L,P<0.001].腹型肥胖MS患者的血清A-FABP水平较非腹型肥胖MS患者显著升高[(15.7±4.2 vs 12.6±5.1)μg/L,P<0.001].血清A-FABP水平与体重指数、腰围、腰臀比、空腹胰岛素、稳态模型评估的胰岛素抵抗指数、空腹血糖、甘油三酯、总胆同醇及平均动脉压等指标均呈正相关(r分别为0.603、0.534、0.411、0.424、0.401、0.370、0.460、0.208和0.522,均P<0.05),而与HDL-C旱显著负相关(r=-0.448,P<0.001).     

脂肪细胞型脂肪酸结合蛋白与代谢综合征相关

Serum adipocyte fatty acid-binding protein (A-FABP) was raised in metabolic syndrome (MS)patients (n= 121) as compared with age-matched healthy subjects [n = 120, (14.7±4.8 vs 6.8 ±3. 0) μg/L,P<0.001]. It reached higher level in MS subjects with visceral obesity [(15.7±4.2 vs 12.6±5.1) μg/L, P<0.001]. Serum A-FABP concentration was positively correlated with body mass index, waist circumference, waist-tohip ratio, fasting insulin, homeostasis assessment for insulin resistance (HOMA-IR), fasting glucose, triglycerides,total cholesterol,and mean arterial blood pressure, whereas negatively correlated with HDL-C (r =-0. 448, P< 0.001).