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.     

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     

Effects of the Trp64Arg polymorphism in the beta3-adrenergic receptor gene on insulin sensitivity in small for gestational age neonates

To evaluate whether the Trp64Arg polymorphism in the beta3-adrenergic receptor (AR) gene is associated with decreased birth weight and might account for some of the association between birth weight and impaired insulin sensitivity, the beta3-AR genotype was assessed in 296 neonates of singleton pregnancies, including 76 neonates classified as small for gestational age (SGA) and 220 neonate classified as appropriate for gestational age (AGA). Fasting glucose and insulin levels were measured on d 3 after birth. The insulin levels and insulin-to-glucose ratio were significantly higher in the SGA group than in the AGA group. Frequency of the Trp64Arg allele was similar in the AGA and SGA groups (0.15 and 0.17, respectively). Moreover, when we adjusted for sex and gestational age, there was no significant difference in birth weight, fasting glucose, insulin levels, or insulin-to-glucose ratio between those with and without the mutation. However, in the SGA group, carriers of the Trp64Arg allele had significantly higher fasting insulin levels and insulin-to-glucose ratios than noncarriers (17.54 +/- 2.11 vs. 13.18 +/- 1.47 microIU/ml, P < 0.05; and 4.89 +/- 0.60 vs. 3.14 +/- 0.42, P < 0.05, respectively), whereas no association was detected for this polymorphism in the AGA group.SGA is an important factor that predisposes to insulin resistance, and the Trp64Arg beta3-AR gene polymorphism may contribute to insulin resistance associated with reduced fetal growth.     

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.     

Association of Trp64Arg polymorphism of the beta3-adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity

OBJECTIVE: To investigate whether Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) gene and Gln223Arg polymorphism of the leptin receptor (Ob-R) gene are associated with obesity in Japanese schoolchildren. DESIGN: Population study of participants from a rural town located within 50 km northeast of Tokyo based on school medical examinations. SUBJECTS: 553 Japanese schoolchildren (291 boys and 262 girls) who were 9-15 y old with a mean age of 11.9 +/- 1.8 y. MEASUREMENTS: DNA was extracted from whole blood and genotyped by PCR-RFLP. Height, weight and blood pressure were measured in school medical examinations. Total cholesterol, triglyceride and HDL-cholesterol concentrations were measured by an autoanalyzer. Obesity index, body mass index (BMI) and LDL-cholesterol concentration were calculated by the respective formulae. RESULTS: In Trp64Arg polymorphism of the beta3-AR gene, the number of obese subjects with Trp/Arg or Arg/Arg genotypes was significantly higher than that of the non-obese subjects (chi2=5.79, P=0.02). The obesity index of subjects with the Arg/Arg or Arg/Trp genotype was significantly higher than that of those with the Trp/Trp genotype (8.2 +/- 18.7% vs 4.5 +/- 15.8%, P=0.04). Moreover, after adjustments for age and gender, BMI of subjects with the Trp/Arg or Arg/Arg genotype was significantly higher than that of those with the Trp/Trp genotype (19.4 +/- 3.6 kg/m2 vs 18.9 +/- 3.2 kg/m2, P= 0.02). However, no significant differences were observed in the clinical characteristics among the genotype groups of the Ob-R gene. CONCLUSIONS: Trp64Arg polymorphism of the beta3-AR gene appears to be a genetic risk factor for obesity in Japanese children, but Gln223Arg polymorphism of the Ob-R gene does not appear to be associated with obesity.     

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is associated with hypertension in men with type 2 diabetes mellitus

A missense mutation of the beta3-adrenergic receptor gene (ADRB3) resulting in a tryptophan/arginine exchange at position 64 (Trp64Arg polymorphism) has recently been associated with greater capacity to gain weight, a low resting metabolic rate, higher blood pressure, and an early onset of type 2 diabetes. These findings prompted us to examine the relationship between this mutation, blood pressure, and vascular complications in German patients with type 2 diabetes. White patients with type 2 diabetes mellitus (n = 417) were enrolled in the study. The Trp64Arg polymorphism of the ADRB3 gene was detected by polymerase chain amplification and subsequent restriction digest with BstN I. Stepwise logistic regression analysis of the entire study population revealed a significant interaction between gender and genotype (P = .019). We therefore performed separate analyses for men and women. There was a significant relationship between hypertension and the ADRB3 Trp64Arg variant in men (P = .015), but not in women. Furthermore, blood pressure levels in male patients with the minor allele had higher blood pressure levels (P < .05), despite a significantly greater number of antihypertensive medications (P = .01). There was no association between ADRB3 genotype and vascular complications in these patients. In conclusion, our data are compatible with a contribution of this genetic variant of ADRB3 to hypertension in male patients with type 2 diabetes. Further studies will be needed to determine the role of this polymorphism as a predictor of hypertension or vascular complications in patients with type 2 diabetes.     

Energy expenditure, body composition and insulin response to glucose in male twins discordant for the Trp64Arg polymorphism of the beta3-adrenergic receptor gene

AIM: The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of the beta3-adrenergic receptor (beta3AR) gene has been associated with an increased prevalence of obesity, insulin resistance and type 2 diabetes. In this, decreased rates of energy expenditure and impaired insulin secretion could play a role. METHODS: In 10 male twin pairs discordant for the Trp64Arg polymorphism, we examined insulin response to glucose by an oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), body composition by the bioimpedance method, dual-energy X-ray absorptiometry scanning and energy expenditure by indirect and direct calorimetry. RESULTS: Twins heterozygous for the Trp64Arg polymorphism showed significantly lower fat mass independent of the method used, and significantly lower fasting insulin and glucose concentrations compared with their homozygous wild-type co-twins. Correspondingly, insulin resistance and insulin secretion determined by homeostasis model assessment were significantly lower in twins carrying the Trp64Arg polymorphism. However, there were no significant differences in adiponectin levels, insulinogenic index assessed by OGTT, or insulin sensitivity, acute insulin response to glucose, glucose effectiveness or insulin disposition index assessed by minimal modelling of the FSIGT. Furthermore, there were no differences in sleeping, resting or post-prandial energy expenditure. CONCLUSIONS: In male twins with a high similarity in genetic and environmental background, the Trp64Arg polymorphism of the beta3AR gene is associated with lower fat mass, fasting insulin levels and an appropriate insulin response to glucose. Thus, heterozygosity for the Trp64Arg variant is unlikely to increase the risk of obesity, insulin resistance or type 2 diabetes.     

Association of beta3-adrenergic receptor gene polymorphism with insulin resistance in Japanese-American men

The Trp64Arg variant of the beta3-adrenergic receptor (beta3-AR) gene is relatively common in Japanese people. We hypothesized that this variant may be associated with obesity and insulin resistance when combined with a westernized lifestyle. To test this hypothesis, we investigated the relationships between the beta3-AR gene variant and obesity and insulin resistance in Japanese-American men, who are known to have a higher prevalence of type 2 diabetes mellitus (DM). The subjects were 152 Japanese-American men living in Hawaii, 83 with normal glucose tolerance (NGT), 40 with impaired glucose tolerance (IGT), and 29 with DM. The frequency of the Trp64Arg allele of the beta3-AR gene was 0.18, almost identical to that of the mainland Japanese. The prevalence of the Trp64Arg allele was 30.1% in NGT, 35.0% in IGT, and 41.4% in DM subjects (nonsignificant). The Trp64Arg variant of the beta3-AR gene showed no significant relationship with obesity or insulin resistance in NGT subjects. However, fasting and 2-hour insulin levels and insulin resistance as determined by homeostasis model assessment (HOMA) were significantly higher in IGT subjects with the Trp64Arg variant. Although indices of obesity were the same in IGT subjects with and without the Trp64Arg variant, differences in the body mass index (BMI) and percent body fat between NGT and IGT subjects were greater for individuals with the Trp64Arg variant. Thus, there is an association between the Trp64Arg variant of the beta3-AR gene and insulin resistance in Japanese-Americans with IGT.     

Tumor necrosis factor alpha gene G-308A polymorphism, insulin resistance, and fasting plasma glucose in young, older, and diabetic Japanese men

In obese subjects, the levels of tumor necrosis factor alpha (TNF-alpha) expression and protein synthesis in adipocytes are increased. A recent study of Caucasians suggested that the TNF-alpha gene promoter region polymorphism at position -308 influences insulin resistance and percent body fat and increases serum leptin levels, although conflicting data are also reported. The present study was performed to investigate the relationship between this polymorphism and the body mass index (BMI), blood pressure, glucose and lipid profiles, and serum leptin in 122 healthy young men aged 21 to 29, 177 older men aged 45 to 65, and 71 type 2 diabetic male patients aged 42 to 78. The BMI, blood pressure, and fasting plasma glucose (FPG), serum lipids, uric acid, insulin, and leptin concentrations were measured. The TNF-alpha G-308A polymorphism was assessed by the polymerase chain reaction restriction fragment length polymorphism method. In the young group, 4 subjects (3.3%) were heterozygous for the TNF2 (G-308A-positive) allele, but there were no significant differences between the TNF1 (wild-type) and TNF2 groups in any measured anthropometric or metabolic parameter. In the older group, the frequency of the TNF2 group was 2.8%, and FPG was significantly higher in the TNF2 versus the TNF1 group (108 +/- 7 v 99 +/- 9 mg/dL, P= .042 by Mann-Whitney Utest). Plasma triglycerides and the insulin resistance index tended to be higher and high-density lipoprotein (HDL) cholesterol tended to be lower in the TNF2 group (P = .06, .20, and .07, respectively), although these differences were not statistically significant. In type 2 diabetic subjects, the frequency of the TNF2 group was also 2.8%, and there were no significant differences between the TNF1 and TNF2 groups in any parameter. HDL cholesterol tended to be lower (P = .10) in the TNF2 group, although it was not statistically significant. In conclusion, no major difference was associated with TNF1 and TNF2 polymorphisms in terms of obesity, blood pressure, lipids, or glucose in young, older, or diabetic Japanese men, although FPG was significantly higher in older men, possibly through increased insulin resistance.     

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.     

Trp64Arg polymorphism of the beta3-adrenergic receptor gene in pregnancy: association with mild gestational diabetes mellitus.

A missense mutation of the beta3-adrenergic receptor gene (Trp64Arg) has been associated with obesity and increased capacity to gain weight in nonpregnant populations. Furthermore, the mutation is a potential modifying factor in the etiology of impaired glucose tolerance and type 2 diabetes. We studied the relation of the beta3-adrenergic receptor genotype to glucose tolerance during pregnancy, a state of physiological insulin resistance. In 179 pregnant women (mean age, 28.5 +/- 0.4 yr), a 2-h oral glucose tolerance test was performed between gestational weeks 20 and 31. The beta3-adrenergic receptor genotype was assessed using restriction fragment length polymorphism. The frequency of the Arg64 allele was 9.15%. In women with mild gestational diabetes (n = 70), as defined by 60 min postload glucose values, the Trp64Arg genotype was more frequent than in women with normal glucose tolerance (n = 109; 26% vs. 11%; P = 0.01). Furthermore, the Trp64Arg polymorphism was associated with increased weight gain during pregnancy (baseline to gestational weeks 20-31) and increased postload glucose, insulin, and C peptide values during the oral glucose tolerance test. The results of the present study extend current knowledge about the association of the Trp64Arg beta3-adrenergic receptor polymorphism with glucose tolerance to a pregnant population. The association with mild gestational diabetes suggests that the impact of the polymorphism may be clinically important during pregnancy, a state of physiological insulin resistance.     

Difficulty in losing weight by behavioral intervention for women with Trp64Arg polymorphism of the beta3-adrenergic receptor gene

OBJECTIVE: Trp64Arg mutation in the beta(3)-adrenergic receptor (beta(3)AR) gene is relatively common in Japanese people. However, it has not been clear whether persons with Trp64Arg mutation in the beta(3)AR gene tend to have obesity and difficulty in losing weight even with a restricted diet and exercise. We investigated the response of body weight and metabolic factors to behavioral intervention in Japanese women with Trp64Arg mutation in the beta(3)AR gene. DESIGN: A 3-month behavioral intervention study using a combination of diet and exercise programs. SUBJECTS: A total of 76 perimenopausal women with no clinical symptoms (age: 54.7+/-7.7 y, body mass index (BMI): 21.0-33.0 kg/m(2)). MEASUREMENTS: Anthropometric measurements (weight, height, body fat, waist circumference, hip circumference, skin fold, resting energy expenditure and blood pressure) and metabolic measurements (serum levels of cholesterol, triglyceride, phospholipid, nonesterified fatty acid, glucose, insulin and leptin) and determination of the beta(3)AR genotype by polymerase chain reaction followed by BstNI digestion. RESULTS: At the baseline of BMI, body weight, body fat, waist circumference, hip circumference, the arm skin fold, resting energy expenditure, or blood lipid and glucose profiles, there was no significant difference in participants with/without mutation of the beta(3)AR gene. The intervention yielded a body weight reduction in 69 and 48%, and induced a significant difference in weight loss (-0.74 and -0.01 kg) for women with wild-type and Trp64Arg mutation, respectively. Significant differences of anthropometric parameters were found in body weight, BMI, waist and hip circumferences and blood pressure of wild type by the intervention. However, women with Trp64Arg mutation did not show significant changes in these anthropometric parameters, except for hip circumference. A significant difference was found in high-density lipoprotein cholesterol (HDL-C) and in the low-density lipoprotein cholesterol/HDL-C ratio in both genotypes. CONCLUSION: The results of the present study suggest that the Trp64Arg mutation of the beta(3)AR gene is associated with difficulty in losing weight through behavioral intervention, although it is not related to obesity-related phenotypes and resting energy expenditure before the intervention.     

Phenotypic characterization of the Trp64Arg polymorphism in the beta3-adrenergic receptor gene in normal weight and obese subjects

Summary The beta₃-adrenergic receptor, located mainly in fat cells of visceral adipose tissue, is involved in the regulation of lipolysis and thermogenesis. Recently, a mutation in the corresponding gene resulting in the replacement of tryptophan by arginine in position 64 (Trp64Arg) has been demonstrated, which associated with obesity and metabolic complications of obesity. We have investigated whether this polymorphism is associated with changes in beta₃-adrenergic receptor function or clinical characteristics in 40 non-obese and 43 obese non-diabetic subjects who underwent elective abdominal surgery. The beta-adrenergic receptor gene polymorphism was examined by restriction-enzyme cleavage conformation. Beta₃-adrenergic receptor function was investigated by measuring lipolysis in isolated visceral white fat cells incubated with noradrenaline (natural ligand) or (CGP) 12177 (selective beta₃-agonist). No homozygotes for the mutation were found. The allelic frequency of Trp64Arg was similar in obese and non-obese subjects (9.4 and 12.5 %, respectively). In obese and non-obese subjects there was no change in body mass index, body fat distribution, fat cell size, fasting circulating levels of insulin, glucose or lipids, blood pressure or adipocyte lipolysis induced by noradrenaline or CGP 12177 when Trp64Arg heterozygotes were compared with Trp64 homozygotes. Our results suggest that the Trp64Arg mutation in its heterozygous form is not a major determinant of beta₃-adrenergic receptor function (when assessed by lipolysis in white adipose tissue) or of the pathophysiology of obesity. [Diabetologia (1996) 39: 857–860] Received: 21 February 1996 and in revised form: 22 March 1996     

Contribution of a missense mutation (Trp64Arg) in beta3-adrenergic receptor gene to multiple risk factors in Japanese men with hyperuricemia.

Epidemiological data reveal that hyperuricemia is a risk factor of atherosclerosis. The risk is possibly caused by a link between hyperuricemia and insulin resistance-related metabolic syndrome. Recently it has been proposed that a missense mutation (Trp64Arg) in the beta3-adrenergic receptor (beta3-AR) gene may contribute to the accumulation of multiple risk factors related to insulin resistance. The present study was undertaken to further clarify an association between the Trp64Arg mutation and the metabolic syndrome in 47 Japanese men with hyperuricemia, who are substantially at high risk of atherosclerosis. One patient (2%) had the homozygous mutation, 12 (26%) were heterozygous for the mutation, and 31 (72%) had no mutation found by the PCR-RFLP analysis. The Trp64Arg mutation was not related to past maximal body mass index (BMI), BMI and waist/hip ratio. The subjects with the heterozygous mutation showed a slightly higher incidence of impaired glucose tolerance and diabetes mellitus in the 75 g oral glucose challenge (67%), as compared with those without the mutation (39%). Serum insulin response at 60 min and the sum of serum insulin in the glucose challenge were greater in the former subjects than those in the latter subjects (P=0.041 and 0.076, respectively). An increase in serum lipoprotein(a) was also observed in the subjects with the heterozygous mutation, but the Trp64Arg mutation was not associated with other dyslipidemia, blood pressure or ischemic changes on the electrocardiogram. These results indicate that the heterozygous mutation of Trp64Arg in the beta3-AR gene partly contributes to the accumulation of multiple risk factors in male subjects with hyperuricemia. A larger prospective study is necessary to elucidate a possible role of the Trp64Arg mutation in atherosclerotic diseases in future.     

蒙、汉族人群小肠脂肪酸结合蛋白基因Ala54Thr多态性的频率

目的:调查蒙、汉族人群小肠脂肪酸结合蛋白(IFABP)基因exonⅡ54位点编码丙氨酸或苏氨酸(A/T)单核苷酸多态性(SNP),探讨不同种族、饮食习惯与IFABP基因多态性频率分布的关系.方法:采用聚合酶链反应(PCR),DNA限制性内切酶酶切及基因测序等技术,分别对208例牧区蒙古族人群、150例张家口市区蒙古族人群和190例汉族人群54A/TIFABP基因型分析.结果:牧区蒙古人群54T等位基因频率为0.51,54A等位基因频率为0.49;市区蒙古族人群54T等位基因频率为0.33,54A等位基因频率为0.67;汉族人群54T等位基因频率为0.30,54A等位基因频率为0.70.与市区蒙古族人群、汉族人群相比,牧区蒙古族人群突变型54T等位基因频率明显增高,且差别有统计学意义(分别为χ2=22.98,P<0.01;χ2=34.23,P<0.01).市区蒙古族和汉族相比较,突变型54T等位基因频率无明显差异(χ2=0.47P>0.05).结论:蒙、汉族人群IFABP基因54A/T多态性频率分布无种族差别;牧区蒙古族人群突变型54TIFABP基因高频率分布可能与高脂饮食习惯有关.     

2 型糖尿病与正常人群中肾上腺素能受体基因Trp 6 4Arg多态性表型特征

目的　研究中国人群 β3 肾上腺素能受体基因 Trp64 Arg错义突变频率 ,并了解该突变对 2型糖尿病临床特征的影响。方法　应用 PCR RFLP技术检测了相互间无一级亲属关系的 12 4例 2型糖尿病患者及 13 8例非糖尿病对照人群中 β3 肾上腺素能受体基因 Trp64 Arg错义突变 ;同时检查体重指数、腰臀比例、血压 ,测定血脂及 OGTT或馒头餐试验中 0分钟及 12 0分钟血糖及胰岛素。结果　非糖尿病人群中 Trp64 Arg等位基因频率为 0 17;突变频率在糖尿病与非糖尿病之间相比无显著性差异 (P >0 0 5 ) ;突变与否间上述临床特征相比无显著性差异 (P >0 0 5 )。结论　该突变至少在其杂合子型可能不是中国人散发 2型糖尿病的主要决定因素 ;纯合子突变型可能导致 2型糖尿病早发 ,有待今后积累资料深入研究。     

The association between Trp64Arg polymorphism of the beta3-adrenergic receptor and autonomic nervous system activity.

The beta3-adrenergic receptor plays a significant role in the control of lipolysis and thermogenesis in brown adipose tissue through autonomic nervous system (ANS) activity. As the Trp64Arg polymorphism of the beta3-adrenergic receptor gene might affect ANS activity, we investigated the association of the polymorphism with ANS activity. The prevalence of the polymorphism was determined in 204 subjects. Ten normal homozygous, 10 heterozygous, and 1 variant homozygous subjects were examined for ANS activity during supine rest and standing by electrocardiogram R-R interval power spectral analysis. Subjects with the variant did not differ from subjects without the variant in body mass index, plasma glucose, plasma insulin, or family history of diabetes or obesity. The total power of heterozygotes at supine rest was lower than that of normal subjects (1124.6 +/- 191.6 vs. 3029.8 +/- 758.8 ms2; mean +/- SE). With a postural change to standing, the parasympathetic and sympathetic nervous system activity indexes of heterozygotes showed a higher response than those of normal subjects (parasympathetic nervous system index, 0.10 +/- 0.02 vs. 0.17 +/- 0.02; sympathetic nervous system index, 10.55 +/- 1.47 vs. 6.26 +/- 1.09), and the difference in total power disappeared. These findings show that subjects with the variant, even the heterozygotes, had lower resting ANS activity than normal subjects.     

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene and obesity in Chinese subjects with components of the metabolic syndrome

BACKGROUND: In regions such as Hong Kong, rapid economic development has led to lifestyle alterations characterized by increases in energy and fat intake and reduction in physical activity. These changes have been associated with a dramatic increase in the prevalence of diabetes and related diseases of the metabolic syndrome. OBJECTIVE: To investigate if a common polymorphism (Trp64Arg) of the beta3-adrenergic receptor gene, previously implicated as predisposing to type 2 diabetes mellitus or obesity in other populations, has a role in the apparent susceptibility of Hong Kong Chinese to diabetes and related disorders. METHOD: A PCR-based protocol was used to genotype 802 Southern Chinese subjects who were either healthy or had one or more of the metabolic disorders including diabetes, hypertension or dyslipidaemia. RESULTS: The frequencies of the mutant A allele (12.7%) and AA genotype (1.7%) did not differ, by the chi2 test, in any patient group with diabetes, hypertension or dyslipidaemia, alone or in combination, compared to healthy controls. Using the t-test in the 802 subjects, those carrying the mutant A allele had evidence of increased obesity with a significantly (all P<0.05) higher body mass index (BMI, kg/m2) and also lower HDL-cholesterol. BMI was also elevated in subjects with the A allele in the separate groups with diabetes, dyslipidaemia or hypertension. Stepwise multiple regression showed this polymorphism to be an independent predictor of BMI. CONCLUSION: These data do not support any direct involvement of the Trp64Arg polymorphism in the development of diabetes, hypertension or dyslipidaemia in Chinese subjects, but do suggest a relationship with obesity.