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 common -675 4G/5G polymorphism in the plasminogen activator inhibitor -1 gene is strongly associated with obesity

Aims/hypothesis. Plasminogen activator inhibitor 1 (PAI-1) increases in several insulin-resistant conditions such as obesity. We tested the hypothesis that the PAI-1 gene might be a candidate for obesity and Type II (non-insulin-dependent) diabetes mellitus. Methods. We investigated the frequency of a common and functional –675 4G/5G promoter polymorphism in the PAI-1 gene in 188 lean, 70 overweight (BMI 25–30 kg/m²) and 247 obese otherwise healthy Scandinavian subjects. Results. The genotypic (p = 0.002), or allelic (p = 0.0004) distribution differed markedly between the three groups. Homozygocity for 4G was more common among obese people, whereas homozygocity for 5G was more common among lean subjects. Heterozygocity was evenly distributed. The lean and overweight groups did not differ in frequency distribution. The relative risk for being obese in comparison to being lean for 4G/4G was threefold higher (p = 0.0003). Also, carriers of the 4G allele in the heterozygous or homozygous form were distributed differently between the three groups (p = 0.006). The 4G carriers were more common among the obese than the lean group. The latter group did not differ from the overweight group. The relative risk of being obese in comparison with lean was twofold increased in 4G carriers (p = 0.0015). Similar results were obtained in men and women. Conclusion/interpretation. Thus, the common –675 4G/5G polymorphism in the PAI-1 gene is strongly linked to obesity and a markedly increased risk for obesity is associated with the 4G allele in its homozygous form. [Diabetologia (2002) 45: ▪–▪] Received: 27 August 2001 and in revised form: 1 October 2001     

脂肪细胞型脂肪酸结合蛋白与胆固醇代谢

脂肪细胞型脂肪酸结合蛋白(FABP4)主要在脂肪组织和巨噬细胞中表达,与脂质分子一起,主要生理作用为参与细胞内部的脂肪酸转运和靶向定位。近来许多研究表明 FABP4与胆固醇代谢关系密切,FABP4可通过影响胆固醇代谢相关的关键基因转录来调节胆固醇的代谢、储存和转运。随着 FABP4抑制剂研究的深入,以 FABP4为靶点的药物有望成为预防和治疗肥胖、2型糖尿病、高胆固醇血症以及动脉粥样硬化等疾病的新策略。     

健脾益肝方对非酒精性脂肪性肝病患者脂肪分布及脂代谢的影响

目的:探讨健脾益肝方对非酒精性脂肪性肝病(NAFLD)患者脂肪分布及脂代谢的影响。方法:将80例NAFLD患者随机分为对照组和治疗组各40例。两组患者均在多学科联合管理下给予个体化的饮食、运动等生活方式指导,治疗组患者在此基础上加用健脾益肝方,疗程均为3个月。通过生物电阻抗技术测量患者治疗前后脂肪质量及分布,定期监测肝肾功能、血脂指标。比较两组患者肥胖、脂肪分布、血脂指标变化。结果:治疗组患者有效率为97.5%,明显高于对照组的82.5%,差异有统计学意义(P<0.05);治疗组患者BMI、BFP、WHR、TC、TG及LDL-C水平明显低于对照组,差异有统计学意义(均P<0.05);治疗组患者躯干及内脏脂肪沉积改善明显优于对照组,差异有统计学意义(均P<0.05)。结论:生活方式干预联合健脾益肝方治疗NAFLD患者能显著改善患者的肥胖及脂代谢紊乱,并且与躯干和内脏脂肪质量的下降密切相关。     

脂肪细胞型脂肪酸结合蛋白与肥胖及代谢综合征

脂肪细胞型脂肪酸结合蛋白(A-FABP)主要在脂肪组织中大量表达,其主要生理作用为参与细胞内部的脂肪酸转运和靶向定位.近期的研究发现,A-FABP是全身胰岛素敏感性以及糖脂代谢的重要调节冈素,与肥胖及代谢综合征的发生发展有紧密联系.     

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.     

The T 54 allele of the intestinal fatty acid-binding protein 2 is associated with a parental history of stroke

To test the hypothesis that the A/T polymorphism of the fatty acid-binding protein 2 gene (FABP2) is associated with impaired lipid metabolism and cardiovascular disease, we compared clinical characteristics and a parental history of cardiovascular disease between 213 sibling pairs discordant for the polymorphism. Siblings with an excess of the T54 allele had higher triglyceride (P = 0.002) and cholesterol (P = 0.019) concentrations than siblings with the A54 allele. Parents of offspring with the T54T and T54A genotypes reported an increased prevalence of stroke compared to parents of offspring with the A54A genotype (P = 0.007). In summary, we have confirmed the association of the FABP2 T54 allele with increased concentrations of cholesterol and triglycerides in genotype-discordant sibling pairs. We also present novel evidence that genetic variation in the FABP2 gene may increase susceptibility to stroke.     

The polymorphisms of UCP2 and UCP3 genes associated with fat metabolism, obesity and diabetes

Uncoupling proteins (UCPs) belong to the family of mitochondrial transporter proteins that may uncouple the transport of protons across the inner mitochondrial membrane from electron transport and the synthesis of ATP from ADP, hence generating heat rather than energy. In mammals, more than five family members have been identified, including UCP1, UCP2, UCP3, UCP4 (or BMCP1/UCP5) and UCP5. The UCPs may play an important role in energy homeostasis and have become prominent in the fields of thermogenesis, obesity, diabetes and free-radical biology and have been considered candidate genes for obesity and insulin resistance. They have been as important potential targets for treatment of aging, degenerative diseases, diabetes and obesity. Recently, a series of studies showed the polymorphisms of UCPs gene association with the fat metabolism, obesity and diabetes. This review summarizes data supporting the roles of UCP2 and UCP3 in energy dissipation, as well as the genetic variety association with fat metabolism, obesity and diabetes in humans.     

Genetic variation of the intestinal fatty acid-binding protein 2 gene in carotid atherosclerosis

The alanine (A) to threonine (T) substitution at codon 54 of the intestinal fatty acid-binding protein 2 (FABP2) has been associated with dyslipidaemia and other characteristics of the metabolic syndrome, which in turn is a risk factor for cerebrovascular disease. The aim of this study was to investigate whether the A54T polymorphism in the FABP2 gene is associated with internal carotid artery (ICA) stenosis in stroke patients. Swedish subjects initially diagnosed with acute cerebrovascular disease (n=196) that had been assessed with ultrasound of the carotid arteries were identified and grouped depending on whether a stenosis was found. The subjects were genotyped for the A54T polymorphism using a PCR-RFLP method. In a multivariate logistic-regression analysis, where known risk factors for atherosclerosis were fixed (diabetes, systolic blood pressure, age and smoking), having the FABP2 T allele was a significant risk factor for ICA stenosis (odds ratio 2.9; 95% confidence interval, 1.1-7.7; p = 0.04) together with diabetes (odds ratio 4.9; 95% confidence interval, 1.8-14; p < 0.01). Age, smoking and blood pressure did not reach statistical significance. In conclusion, our result supports the hypothesis that the FABP2 A54T polymorphism is associated with ICA stenosis.     

Codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with increased fat oxidation and hyperinsulinemia, but not with intestinal fatty acid absorption in Korean men

The alanine to threonine substitution at codon 54 (Ala54Thr) of the fatty acid binding protein 2 (FABP2) gene has been reported to be associated with increased fat oxidation and insulin resistance in several populations. It has been hypothesized that Ala54Thr substitution results in enhanced intestinal uptake of fatty acids and thereby an impairment of insulin action, but this hypothesis has not been proven in vivo. We studied the association between the Ala54Thr polymorphism of the FABP2 gene and intestinal (3)H-oleic acid absorption, as well as basal insulin level, basal metabolic rate, and fat oxidation rate in 96 healthy young Korean men. Among our subjects, the allele frequency of the Ala54Thr substitution was 0.34. Subjects with Thr54-encoding allele were found to have a higher mean fasting plasma insulin concentration and a higher basal fat oxidation rate compared with the subjects who were homozygous for the Ala54-encoding allele. However, there was no significant difference in basal metabolic rate or (3)H-oleic acid absorption according to the FABP2 gene polymorphism. These results suggest that the Ala54Thr substitution in the FABP2 gene is associated with increased fat oxidation and hyperinsulinemia in normal Korean men, but these effects are not mediated by an increase in the intestinal fatty acid absorption.     

Association between Ala54Thr substitution of the fatty acid-binding protein 2 gene with insulin resistance and intra-abdominal fat thickness in Japanese men

Summary Alanine to threonine substitution at codon 54 of the fatty acid-binding protein 2 (FABP2) gene was recently shown to be associated with insulin resistance in Pima Indians. It has been hypothesized that the mutation may result in enhanced intestinal uptake of fatty acids, and thereby an impairment of insulin action. We analysed the association of the Ala54Thr substitution with insulin sensitivity and abdominal fat thickness in 395 Japanese men aged 50.5 ± 8.8 years (mean ± SD) with a body mass index of 24.4 ± 3.0 kg/m². The frequency of the Thr54 allele was 0.34. Although the polymorphism was not significantly associated with diabetes or impaired glucose tolerance, subjects homozygous for the Thr54 allele had higher basal insulin levels. Analysis by homeostasis model assessment showed an association between the amino acid substitution and greater insulin resistance, and slightly higher beta-cell function. Oral glucose tolerance tests performed in 392 subjects without fasting hyperglycaemia showed higher 2-h insulin concentrations in individuals homozygous for the Thr54 allele when compared with heterozygotes or homozygotes for the Ala54 allele. No significant association was obtained between the polymorphism of the FABP2 gene and body mass index. However, ultrasound measurements of abdominal fat thickness revealed a greater accumulation of intra-abdominal fat in subjects homozygous for the Thr54 allele, whereas subcutaneous fat thickness was not associated with the polymorphism. These observations suggest that the Ala54Thr substitution in the FABP2 gene is associated with insulin resistance in Japanese men, and that visceral fat accumulation might be involved in the impaired insulin action associated with the substitution. [Diabetologia (1997) 40: 706–710] Received: 30 December 1996 and in revised form: 10 March 1997     

LEPR外显子突变与ApoE基因多态性对儿童脂代谢的影响

目的 探讨瘦素受体（LEPR）外显子突变与载脂蛋白（Apo）E基因多态性对儿童脂代谢的影响。方法选择肥胖儿童178例（肥胖组）和非肥胖但超重的健康儿童136例（对照组）。空腹12h后抽取静脉血,测定两组血清血脂（TC、TC、HDL—C、LDL—C）水平,采用PCR—RFLP及聚丙烯酰胺凝胶电泳分析LEPR的20外显子基因突变频率,并对受试者ApoE基因型进行分析;测量两组身高、体质量,计算BMI、脂肪百分比（％fat）。结果LEPR基因第20外显子检出基因型A／A型、A／G型、G／G型。ApoE基因型检出E3／3、FA／3、E2／3、FA／2。肥胖组LEPR基因第3057位D→A突变频率、ApoE基因中磁、E4等位基因频率高于对照组。肥胖组TG、BMI及％fat水平高于对照组,HDL-C水平低于对照组。结论肥胖儿童LEPR基因第20外显子发生基因突变与ApoE基因存在基因多态性,明显影响其脂质代谢和体脂分布。     

Plasma adipocyte and epidermal fatty acid binding protein is reduced after weight loss in obesity

AIM: Plasma adipocyte fatty acid binding protein (A-FABP) and epidermal fatty acid binding protein (E-FABP) concentrations have been linked to obesity and the metabolic syndrome. In this study, we investigated whether plasma A-FABP and E-FABP concentrations are altered by weight loss in obese patients. METHODS: In a prospective study, fasting plasma A-FABP and E-FABP concentrations were measured before and 6 months after gastric banding in 33 morbidly obese patients, with a body mass index (BMI) of 46 +/- 5 kg/m(2). Eleven healthy subjects with a BMI < 25 kg/m(2) served as controls. RESULTS: A-FABP and E-FABP plasma concentrations were higher in obese subjects (36.7 +/- 6.7 and 3.7 +/- 0.7 ng/ml, respectively) than in controls (18.1 +/- 0.6 and 2.6 +/- 0.5, respectively, p < 0.01). Gastric banding reduced BMI to 40 +/- 5 kg/m(2), A-FABP to 32.6 +/- 5.4 ng/ml and E-FABP to 1.9 +/- 0.7 ng/ml (all p < 0.05) after 6 months. Insulin sensitivity as estimated by the Homeostasis Model Assessment insulin resistance index was unchanged. A-FABP concentrations were significantly associated with BMI before and 6 months after surgery (p < 0.05, r = 0.42 and r = 0.37 respectively). CONCLUSIONS: Elevated plasma A-FABP and E-FABP concentrations in morbidly obese subjects are reduced after gastric banding-induced weight loss. This suggests that FABP may be associated with improvement of metabolic conditions over time.     

Gln27Glu variant of the beta2-adrenergic receptor gene is not associated with obesity and diabetes in Japanese-Americans

The beta(3)-adrenergic receptor (AR) gene variant (Trp64Arg) has been reported to be associated with obesity and insulin resistance in humans. However, this association remains controversial. We investigated the relationships between the beta(2)-AR gene variant (Gln27Glu) and obesity, insulin resistance, and serum lipids in Japanese-Americans. The frequency of an abnormal Gln27Glu allele in the beta(2)-AR gene in 652 subjects was 0.092 in males, 0.077 in females, and 0.084 overall, markedly lower than the previously reported value of 0.4 in Caucasian men and women. In both males and females, there were no differences in the indices of obesity, insulin resistance, and serum lipid levels between the subjects with and without the beta(2)-AR gene (Gln27Glu) variant in patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes (DM). The frequency of the beta(2)-AR gene (Gln27Glu) variant tended to increase with worsening of glucose tolerance, but the differences were not statistically significant. Furthermore, there were no differences in the frequency of the beta(2)-AR gene variant in either males or females with obesity (body mass index [BMI], > or = 25.2). Even in Japanese-Americans, who have a more westernized life style than Japanese, the association of the beta(2)-AR gene (Gln27Glu) variant with the parameters of obesity, insulin resistance, and serum lipid level has yet to be clarified. We conclude that the beta(2)-AR gene (Gln27Glu) variant might not be an important factor for obesity or IGT in Japanese subjects.     

The ALDH2 gene rs671 polymorphism is not associated with essential hypertension

Essential hypertension (EH) is a worldwide problem. Acetaldehyde dehydrogenase 2 (ALDH2) gene has been suggested to be correlated with EH. However, the results are inconsistent. This study aimed to investigate the associations of ALDH2 rs671 polymorphism with EH in a Chinese Han population in Shanghai. Genotype of ALDH2 rs671 was analyzed in 1923 EH patients and 1115 control subjects. We found no association between ALDH2 rs671 and EH risk or EH-related quantitative blood chemistry values. Furthermore, a meta-analysis was performed and the summary results from 11220 patients and 8339 control subjects were consistent with our findings. These results indicated that rs671 of ALDH2 may not associate with the risk of EH.