瘦素受体基因Lys109Arg多态性与非酒精性脂肪性肝病的关系

目的探讨瘦素受体基因Lys109Arg多态性与非酒精性脂肪性肝病(NAFLD)的关系。方法收集180 例接受体检的成年人,分成2组:(1)NAFLD组117例,男77例,女40例,平均年龄(50．4±13．1)岁;(2)对照组63例,男32例,女31例,平均年龄(49．1±14．5)岁。同时测定身高、体重、臀围、腰围、腹壁脂肪厚度、体脂含量、血压。入选对象均签署知情同意书。试验对象进行空腹采血,血标本用于检测丙氨酸氨基转移酶、甘油三酯、高密度脂蛋白和血糖水平。结果NAFLD患者和正常对照组LEPR基因Lys109Lys、Lys109Arg和Arg109Arg多态性分布差异无统计学意义(x2=1．409,P=0．494)。腹壁脂肪厚度LEPR基因Lys109Lys携带者平均为(4．1± 0．4)cm,Lys109Arg平均为(2．8±0．6)cm,Arg109Arg平均为(2．7±0．7)cm,LEPR基因Lys109Lys携带者明显高于Lys109Arg和Arg109Arg携带者,差异有统计学意义(F 5．197,P=0．006)。血清胆固醇水平LEPR 基因Lys109Lys携带者平均为(5．1±0．4)mmol／L,Lys109Arg平均为(25．5±6．9)mmol／L,Arg109Arg平均为(27．2±8．4)mmol／L,LEPR基因Lys109Lys携带者明显降低,差异有统计学意义(F=8．164,P=0．005)。结论瘦素受体基因Lys109Arg多态性可能参与腹壁脂肪的分布和胆固醇代谢的调节,至于是否参与NAFLD的发病机制尚待进一步研究。     

Tumor necrosis factor-alpha--308 G/A polymorphism in obese Caucasians

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism in the 5'-flanking region of the TNF-alpha gene (G-308A) has been reported to be more frequent in obese than in lean subjects and has also been associated with increased expression of this cytokine in fat tissue and influences fat mass and insulin resistance. We, therefore, examined the relationship between this variant and obesity in a German Caucasian population. SUBJECTS AND METHODS: We genotyped 176 index subjects recruited within the framework of the BErG (Berlin Ern?hrung Geschwister)- Study for the TNF-alpha-G-308A polymorphism. Subjects were characterized for weight, height, waist and hip circumference, body mass index (BMI), body composition, glucose tolerance, leptin and angiotensinogen levels. RESULTS: The frequency of the -308A allele (0.18) was similar to that reported previously and genotype distribution was in Hardy-Weinberg equilibrium (GG, n=118; GA, n=53; AA, n=5). There was a significant difference in allele frequencies of the polymorphism by BMI quartiles (I,<27.3 kg/m2; II, 27.3-31.9 kg/m2; III, 31.9-36.5 kg/m2; IV,>36.5 kg/m2, in each quartile n=44) with -308A allele carriers having a higher BMI than G allele carriers (P=0.013). Despite previous smaller studies that have related insulin resistance to the G-308A polymorphism, we found no relationship between glucose and insulin response during an oral glucose tolerance test (OGTT) and the polymorphism. Furthermore, none of the plasma parameters were related to the polymorphism. CONCLUSION: Our findings support the hypothesis that the G-308A polymophism of the TNF-alpha gene is associated with BMI. The G-308A polymorphism may, therefore, represent a genetic marker for increased susceptibility for obesity in Caucasians.     

Effects of moderate consumption of white wine on weight loss in overweight and obese subjects

BACKGROUND: Patients on dietary, weight-reducing treatment commonly are advised against alcohol consumption. In light of the widespread use of alcoholic beverages and the well-established benefits of light to moderate alcohol consumption in risk reduction, a revision of dietary treatment recommendations may be warranted. OBJECTIVE: To investigate whether daily consumption of moderate amounts of alcohol influences the effectiveness of an energy-restricted diet in overweight and obese subjects. DESIGN: A prospective randomized clinical trial was conducted, with a 3-months intervention period and two isocaloric dietary regimens containing 6.3 MJ (1500 kcal) each, one with 10% of energy from white wine and one with 10% of energy from grape juice. The trial was performed in obese subjects being recruited from the Obesity Outpatient Clinic at the University Hospital, Ulm, who all habitually consumed moderate amounts of alcohol. Out of 87 patients, 49 were eligible to participate and 40 completed the study (age 48.1+/-11.4 y, BMI 34.2+/-6.4 kg/m(2)). Efficacy parameters were body weight and biomarkers of good health. RESULTS: All subjects achieved significant body weight reduction. Weight loss in the grape juice group and white wine group was 3.75+/-0.46 and 4.73+/-0.53 kg, respectively. Percent body fat, waist circumference, blood pressure, blood glucose, insulin, triglycerides, and cholesterol were reduced. The antioxidant status was unchanged, as were liver enzyme activities and other safety parameters. There were no significant differences between the groups. CONCLUSIONS: An energy-restricted diet is effective in overweight and obese subjects used to drinking moderate amounts of alcohol. A diet with 10% of energy derived from white wine is as effective as an isocaloric diet with 10% of energy derived from grape juice.     

TNF-alpha -308G>A polymorphism modulates cytokine serum concentrations and macrovascular complications in diabetic patients on aspirin.

BACKGROUND: Tumor necrosis factor (TNF)-alpha has pleiotropic effects in cytokine-mediated inflammation underlying atherogenesis. Activation of this inflammatory process is assumed to be different in diabetic and non-diabetic individuals. Previous studies in non-diabetic subjects showed no association between TNF-alpha -308G>A polymorphism and coronary artery disease. METHODS: Vascular complications and cytokine serum concentrations were assessed as a function of the TNF-alpha -308G>A polymorphism in 76 diabetic patients on low-dose aspirin. RESULTS: Of 76 adult diabetic patients, 18 (24%) carried the TNF-alpha -308A allele (17 AG, 1 AA) and 58 (76%) carried wild-type alleles (GG). Prevalence of macrovascular complications was 33% in TNF-alpha -308A allele carriers (AG+AA) and 78% in wild-type allele carriers (GG) (p<0.001). In contrast, prevalence of microvascular complications was 78% and 84%, respectively, and did not significantly differ between the study groups. TNF-alpha -308A allele carriers (AG+AA) compared to wild-type allele carriers (GG) had significantly lower median serum concentrations of hs-C-reactive protein (1.5 vs 2.9 mg/L, p=0.030), interleukin 1-beta (0.9 vs 1.2 ng/L, p=0.046), and interleukin-6 (3.6 vs 4.9 ng/L, p=0.023). In multiple regression analysis, the prevalence of macrovascular diabetic complications was significantly associated with TNF-alpha -308G>A polymorphism (p<0.001) and serum concentrations of HDL-cholesterol (p=0.007) while confounding effects of further variables were excluded. CONCLUSION: TNF-alpha -308G>A polymorphism modulates cytokine serum concentrations and macrovascular complications in diabetic patients on aspirin. Diabetic carriers of the TNF-alpha -308A allele might benefit more from a prophylaxis with low dose aspirin than non-carriers.     

A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with lower levels of body mass index and glycaemia in a population-based sample of 5857 middle-aged White subjects.

AIMS: The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2-243A-->G polymorphism and levels of body mass index (BMI) and estimates of glycaemia. METHODS: Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2-243A-->G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects. RESULTS: The G-allele was associated with modestly lower BMI (P = 0.01). In a case-control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m2 was 19.5% (18.4-20.6) compared with 17.1% (15.5-18.8) in 968 participants having BMI > or = 30 kg/m2 (P = 0.03), odds ratio 0.9 (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n = 206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383) 5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). CONCLUSION: The present study suggests that the GAD2-243A-->G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.     

The effects of uncoupling protein-1 genotype on lipoprotein cholesterol level in Korean obese subjects

Uncoupling protein-1 (UCP-1) plays a major role in thermogenesis, and has been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of A-3826G polymorphism of the UCP-1 gene on the plasma lipid profiles in 190 Korean obese subjects with a body mass index (BMI) more than 30 kg/m2. Height, weight, BMI, wait-to-hip ratio (WHR), obesity index, and body composition were measured and genotype of UCP-1 was analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method. Serum concentrations of fasting glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride were measured. The frequencies of UCP-1 genotypes were AA type, 22.1%; AG type, 53.7%; and GG type, 24.2%; and the frequency of G allele was 0.51. Among many parameters, diastolic blood pressure (DBP) (P = .023) and low-density lipoprotein (LDL) cholesterol (P = .011) were significantly higher in AG and GG types compared with AA type, whereas HDL cholesterol was significantly lower in GG type compared with other types (P < .05). Atherogenic index was significantly higher in GG type compared with AA type (P = 0.027). LDL-to-HDL cholesterol ratio was significantly increased in the order of AA < AG < GG types (P = .001). When the subjects were divided into a normal group and a hyper-LDL cholesterolemia group by LDL cholesterol level of 3.626 mmol/L (140 mg/dL), the frequency of hyper-LDL cholesterolemia was significantly higher in GG type compared with other types by Fisher's exact (chi-square) test (P = .05). When logistic regression analysis was conducted to find the risk factors of hyper-LDL cholesterolemia, the odds ratio was 4.115 (P = .03) for GG type of UCP-1 gene. These results suggest that the GG type of the UCP-1 gene has a strong association with increased LDL cholesterol level and might be a significant risk factor for hyper-LDL cholesterolemia among Korean obese subjects.     

Tumor necrosis factor [alpha ] -238 and -308 polymorphisms do not associate with insulin resistance in hypertensive subjects

It is well established that, as a group, patients with essential hypertension are characterized by insulin resistance. Previous studies have shown that a biallelic polymorphism in the tumor necrosis factor (TNF)alpha promoter position -308 and -238 might be involved in the insulin resistance state in diabetic and/or nondiabetic subjects. We determined these polymorphisms in 235 nondiabetic hypertensive subjects and 246 unrelated normotensive controls. Fasting plasma glucose, insulin, lipoprotein, leptin, and TNFalpha concentrations were measured, in addition to plasma glucose and insulin responses to a 75-g oral glucose tolerance test (OGTT). Insulin sensitivity was also determined by an insulin suppression test in 69 hypertensive and 76 normotensive individuals. The results showed no association of these genotypic distributions between hypertensive and normotensive individuals both at -308 (GG, GA, and AA were 80.9%, 17.9%, and 1.3% in hypertensives, 84.2%, 15.4%, and 0.4% in normotensives, chi(2) = 1.68, P =.432) and at -238 (GG, GA, and AA were 98.3%, 1.7%, and 0% in hypertensives, 96.7%, 3.3%, and 0% in normotensives, chi(2) = 1.19, P =.276) sites. These results did not change even after adjustment for values of age and body mass index (BMI). Anthropometric measurements, fasting plasma glucose, insulin, lipoprotein concentrations, glucose, and insulin responses to OGTT, TNFalpha, and leptin concentrations were similar between the genotype at the -308 site both in hypertensive and normotensive groups. Insulin sensitivity, either measured by an insulin suppression test or homeostasis model assessment (HOMA) index, did not differ between the genotype at the -308 site in subjects with hypertension or normotension. Fasting plasma TNFalpha (10.2 alpha 0.5 pg/mL v 10.1 +/- 0.5 pg/mL, P =.928) concentrations did not differ between hypertensive and normotensive subjects even after adjustment for body fat and BMI values. We conclude that TNFalpha promoter gene polymorphisms at position -238 and -308 do not play a major role in the pathogenesis of insulin resistance in Chinese subjects with or without hypertension.     

肿瘤坏死因子-α基因G-308A位点多态性变化与儿童肥胖易感性的关系

目的 通过分析肿瘤坏死因子TNF-α基因G-308A位点单核苷酸多态性（SNP）在正常和肥胖儿童的分布频率,探讨G-308A位点SNP与儿童肥胖症的关系.方法 2007年1月至2008年12月,从长沙市开福区5所小学6～13岁的儿童中根据年龄分层按随机数字表法选取147例肥胖组和118名正常对照组儿童,分别测定腰围、臀围、腰臀比、体脂百分比、血压、血脂、血糖和血浆TNF-α等,计算稳态模型胰岛素抵抗指数.应用聚合酶链反应-限制性片段长度多态性方法检测TNF-α基因G-308A位点多态性.计数资料用卡方检验,组间比较采用t检验或方差分析.结果 肥胖组儿童TNF-α水平[（171±34） ng/L]高于正常组儿童（（91 ±22） ng/L,t=8.855,P＜0.01）,TNF-α基因G-308A位点肥胖组和正常组等位基因A的突变率分别为10.6％与6.8％,两组间基因频率（x2=2.296,P＞0.05）和基因型频率比较差异无统计学意义（x2=2.082,P＞0.05）;各基因型间的TNF-α水平、腰围、腰臀比、收缩压、体脂百分比、总胆固醇、低密度脂蛋白胆固醇、空腹血糖、空腹胰岛素、稳态模型胰岛素抵抗指数比较差异无统计学意义（均P ＞0.05）.结论 TNF-α基因G-308A位点的SNP与儿童肥胖的发病无相关性.     

Angiotensinogen gene polymorphism (Met235Thr) influences visceral obesity and insulin resistance in obese Japanese women

To investigate the relationship between angiotensinogen (AGT) Met235Thr polymorphism (M235T) and human obesity, because AGT is regarded as one of the cytokines produced from adipocytes and serum AGT concentrations are reported to be positively correlated with body mass index. One hundred and twenty obese Japanese women (age, 58.8+/-9.4 years; body mass index, 32.2+/-4.9 kg/m(2)) were enrolled. Angiotensinogen genotypes were determined with a fluorescent allele-specific DNA primer assay system. Subjects were divided into M/M, M/T, and T/T groups. Control subjects comprised 146 healthy age-matched women. Clinical characteristics and the effects of diet and exercise therapy for 6 months were compared among the 3 genotypes. The genotype frequencies of AGT M235T polymorphism were in accordance with the Hardy-Weinberg equation (obese: M/M, 6.7%; M/T, 27.5%; T/T, 65.8%; control: M/M, 6.8%; M/T, 21.2%; T/T, 71.9%). The frequency of the T allele did not differ between obese and control subjects (0.80 vs 0.83). As the number of obese women with M/M genotype was only 8, comparisons of the characteristics and outcomes of weight reduction therapy were performed only between subjects with M/T genotype and T/T genotype. In the T/T group, % body fat and waist circumference at baseline were significantly greater than in the M/T group (36.3%+/-4.8% vs 33.8%+/-4.7%, P=.0105; 107.9+/-10.9 vs 102.6+/-7.9 cm, P=.0428, respectively). Before the weight reduction therapy, significantly higher insulin and higher homeostasis model assessment (HOMA-R) were demonstrated in the T/T group than in the M/T group (9.1+/-5.5 microU/mL vs 5.9+/-4.4 microU/mL, P=.0056; 2.3+/-1.4 vs 1.6+/-1.3, P=.0252, respectively). Both systolic and diastolic blood pressure at baseline in the T/T group tended to be higher than those in the M/T group, but the differences were not significant. No genotype-dependent difference in energy expenditure or outcome of weight reduction therapy was observed with respect to AGT M235T polymorphism. After the diet and exercise therapy, the blood pressure in the T/T group tended to be higher than that in the M/T group, but the difference was not significant. We demonstrated that the T/T genotype of the AGT M235T gene polymorphism was positively related to visceral obesity and hyperinsulinemia in obese Japanese women. Blood pressure did not show genotype-specific differences before or after the treatment. Further studies of the association between obesity and this gene polymorphism should contribute to understanding and treating obesity-related diseases.     

Soy compared to casein meal replacement shakes with energy-restricted diets for obese women: randomized controlled trial

Recent studies suggest that obese individuals lose weight more rapidly and lose more total weight with soy protein than with animal protein as a major diet component. The purpose of the present study was to evaluate the weight-loss efficacy and changes in body composition, waist circumference, blood pressure, and levels of plasma glucose, insulin, serum lipids, C-reactive protein, and homocysteine from consumption of either 3 soy shakes or 3 casein shakes daily as part of a 16-week, energy-restricted diet for obese women. Forty-three women with body mass index values of 30 to 40 kg/m(2) were randomized to intensive dietary interventions using either casein (n = 21) or soy (n = 22) shakes. Subjects were instructed to consume 3 shakes, 1 prepackaged entrée, and 5 servings of fruits or vegetables daily to achieve an energy intake of 4.5 to 5.0 MJ/d. Subjects attended classes weekly or biweekly. Weight, body fat, lipid, and glucose measurements were obtained at baseline and at 8 and 16 weeks. For both groups combined, subjects lost 8.1% of initial body weight (7.7 kg) at 8 weeks and 13.4% (12.7 kg) at 16 weeks. Weight loss from baseline did not differ significantly by group and, for completing subjects, was 14.0% +/- 1.2% (mean +/- SE) for casein and 12.8% +/- 1.4% for soy. With the intention-to-treat analysis, weight losses at 16 weeks were 12.5% +/- 1.4% for casein and 11.3% +/- 1.2% for soy. Body fat losses were 23.7% +/- 2.0% for casein and 21.8% +/- 2.4% for soy and did not differ significantly. Both study groups lost significant amounts of weight with a highly structured behavioral program incorporating 4 meal replacements and vegetables and fruits. Differences in weight loss and body composition changes between casein and soy treatments were not significant.     

TNF-α-308位点多态性与肺癌易感性关系的Meta分析

目的 系统评价TNF-α-308多态性与肺癌发病风险的相关性.方法 计算机检索PubMed、EMbase、WanFang、CNKI,查找国内外关于TNF-α-308多态性与肺癌易感性关系的病例对照研究,检索时限为建库至2014年2月20日.由2名评价者根据纳入与排除标准筛选文献,提取并评价资料后,采用RevMan 4.2软件及Stata 10.0软件进行Mete分析.结果 最终纳入13个研究,其中包括病例组患者1904例,对照组正常人1699例,经异质性检验,各研究间无统计学异质性（P＞0.1）固定效应模型Meta分析结果显示：对于总体人群而言,TNF-α-308与肺癌易感性关联有统计学意义（OR=1.74,95％ CI：1.17 ～ 2.57,P=0.006）.在研究人群种族基础上进行亚组分析显示：在高加索人群中,TNF-α-308与肺癌易感性关联无统计学意义（OR=0.97,95％ CI：0.56～1.66,P=0.91）;在亚洲人群中,TNF-α-308与肺癌易感性关联有统计学意义（OR=3.08,95％ CI：1.51～6.26,P=0.002）.结论 在亚洲人群中,TNF-α-308位点可能是增加肺癌患病风险的危险因素,在高加索人群中,TNF-α-308多态性与肺癌的发病风险不存在相关性.     

Body weight changes and the A-6G polymorphism of the angiotensinogen gene

BACKGROUND: The objective of the study was to analyze the relationship of polymorphisms of the angiotensinogen gene with changes in body weight during 3 y of antihypertensive treatment, in a group of young adults with essential hypertension. METHODS: Essential hypertensives, less than 50 y old, never previously treated with antihypertensive drugs and in the absence of diabetes mellitus were included. After the initial evaluation, patients were treated using only non-pharmacological measures (n=29), beta-blockers (n=40) or angiotensin-converting enzyme inhibitors (n=66). Resting blood pressure, biochemical profile and body weight at the beginning and yearly were measured. The polymorphism A-6G of the angiotensinogen gene located in the promoter region was analyzed. RESULTS: One-hundred and thirty-five patients were included. Genotypes of the A-6G polymorphism of the AGT gene were in Hardy-Weinberg equilibrium (AA 34, AG 63, GG 38). No significant differences were observed among genotypes in terms of age, body mass index, body weight, systolic or diastolic blood pressure. No significant differences in the genotype distribution or in the allele frequencies were observed, although the A allele was most frequent among the obese subjects. During the 3 y of antihypertensive treatment, there was a trend to increase weight despite the dietary recommendations. The slopes of body weight over time, adjusted by age and baseline BMI, differed significantly among the homozygote genotypes (P=0.006). The highest were for those with the AA genotype and the lowest for the GG genotype (1.180+/-0.25 and -0.128+/-0.24 kg/y; P=0.0001). The influence of the genotype in the changes on body weight remained significant after considering its interaction with the kind of antihypertensive treatment, although among subjects carrying the AA genotype those treated with ACEi showed the least body weight change. Furthermore, A-6G genotypes had the largest influence on weight changes, accounting for 19% of the variance, when age, sex and initial body mass index were included in the model. CONCLUSIONS: In a group of young adult hypertensive subjects, there was a trend to increase weight despite dietary recommendations. Subjects with the AA genotype were those with the largest weight gain, but this effect was modified by the antihypertensive treatment.     

The interaction between the interleukin 6 receptor gene genotype and dietary energy intake on abdominal obesity in Japanese men

Previous reports have shown that the Asp358Ala (T/G) polymorphism of the interleukin 6 receptor (IL6R) gene is associated with obesity and type 2 diabetes mellitus, but few studies have examined this association in the Japanese population. We performed the current study to investigate the relationship between the IL6R Asp358Ala (T/G) polymorphism and obesity in healthy Japanese men. Two hundred eighty-five healthy Japanese men (age, 46.1 +/- 11.5 years [mean +/- SD]; waist circumference [WC], 83.9 +/- 9.3 cm; body mass index, 23.3 +/- 3.3 kg/m(2)) employed by a Japanese company were enrolled in this study. Height, weight, and WC were measured, and daily energy intake levels were assessed by self-reported questionnaires. Genotyping of polymorphisms was performed by using melting curve analysis; no association was found between IL6R genotype and WC or body mass index. However, when the subjects were stratified by IL6R genotype, an association between WC and dietary energy intake level was found in the TT + GT-type subjects (P for linear regression = .048), but not in GG subjects (P for linear regression = .555). In addition, logistic regression analysis revealed that the interaction of IL6R (GG vs TT + GT) genotypes and dietary energy intake levels affected risk for abdominal obesity (P for interaction = .030). We concluded that the IL6R Asp358Ala (T/G) polymorphism appears to interact with energy intake and affect abdominal obesity in Japanese men. The interaction of this genotype and energy intake warrants further study.     

5-HT2A receptor gene polymorphism is associated with food and alcohol intake in obese people

OBJECTIVE: To test the association between a polymorphism of the 5-HT2A receptor gene, -1438G/A, and energy and nutrients intake, including alcohol. SUBJECTS: Two hundred and seventy six unrelated overweight subjects (180 women, 96 men) were recruited from the Nutrition Department of Bichat Hospital in Paris on the basis of 120% of ideal body weight (body mass index, BMI=33.3+/-4.8 kg/m2). A second overweight sample (31 women, 49 men) was drawn from the Stanislas Family Study, composed of volunteers for a free health examination in Nancy (BMI=29.6+/-3.1 kg/m2). MEASUREMENTS: Energy and nutrients intake were assessed using the diet history method in Paris and the 3-day record method in Nancy. We analyzed the polymorphism by PCR followed by MspI digestion. Statistical differences between genotypes were assessed by using the non-parametric Kruskal-Wallis test. RESULTS: In the whole overweight population, the A allele was associated with lower energy intake 10. 3+/-2.8, 9.9+/-2.8, 9.3+/-2.9 MJ/day for GG, GA and AA genotypes respectively (P<0.05). This association was significant in the patient sample from Paris and in the overweight male volunteers from Nancy. Allele A-related lowering in energy intake was due to a trend to lower intakes in all the main nutrients. The A allele was also associated with a lower alcohol consumption: 18.4+/-19.7, 15.3+/-21. 2 and 12.3+/-17.5 g/day for GG, GA and AA genotypes, respectively (P<0.05). CONCLUSIONS: These data indicate that a gene polymorphism may influence food and alcohol intake in overweight humans. This could be explained by the role of the serotonergic system as a determinant of food intake.     

Association of polymorphisms in the estrogen receptor alpha gene with body fat distribution

OBJECTIVE: To examine whether polymorphisms of the estrogen receptor (ER) alpha gene are associated with body fat distribution. DESIGN: Cross-sectional, epidemiological study of two single-nucleotide polymorphisms, a T --> C (PvuII) and an A --> G (XbaI), in the first intron of the ERalpha gene. SUBJECTS: A total of 2238 community-dwelling middle-aged and elderly Japanese population (age: 40-79 y). MEASUREMENTS: The ERalpha genotypes (by automated fluorescent allele-specific DNA primer assay system), anthropometric variables, fat mass (FM) and percentage FM (%FM) (by dual-energy X-ray absorptiometry). RESULTS: FM and waist were inversely associated with age (r=-0.630 and -0.504, respectively) in women with the GG genotype. On the other hand, waist circumference of the AA genotype was positively correlated with age (r=0.231). Thus, for middle-aged women (40-59 y) with the AG or GG genotype body mass index (BMI), %FM, FM, waist, hip and waist-to-hip ratio (WHR) were larger than those with the AA genotype. In particular, FM and waist were greater by 20% and 9%, respectively, for the GG genotype, compared to the AA genotype. Alternatively, FM and waist were smaller by 18% and 6%, respectively, in older women with the GG genotype, compared to the AA genotype. No effect was found among the A --> G polymorphisms for men. For both genders, no difference was found in any variables among the TT, TC and CC genotypes with the exception of BMI of older men (60-79 y). CONCLUSION: No association was found between the ERalpha gene polymorphisms and body fat distribution in men. For women, the A --> G polymorphism, in particular the GG genotype, may contribute to the development of upper-body obesity in middle-aged individuals, but may serve to decrease the whole-body and abdominal fat tissue of older individuals.     

360His polymorphism of the apolipoproteinA-IV gene and plasma lipid response to energy restricted diets in overweight subjects

Obesity is commonly associated with high rates of cardiovascular disease (CVD). Weight loss in obese subjects reduces risk factors for CVD but this response is not uniform. Genetic factors could be involved in this variability. The 360His polymorphism of apolipoproteinA-IV (apoA-IV) influences the lipid response to fat intake, but it is unclear whether this polymorphism could contribute to lipid variability during weight loss. Therefore, we assessed the effects of an energy restricted diet (6.3 MJ) for 12 weeks on weight loss and plasma lipids according to apoA-IV genotype in 186 overweight/obese subjects (BMI mean 33+/-4.3, range 25.0-48.0 kg/m(2)). The frequency of the 360His allele was 0.083. Energy restriction for 12 weeks resulted in an average weight loss of 8. 25+/-0.28 kg. HDL-C increased 5.4% in subjects with the apoA-IV-1/1 genotype with weight loss compared to a 2.6% decrease in apoA-IV-1/2 subjects (P=0.035). This was more apparent when only the subjects with type 2 diabetes (n=57) were analyzed (P=0.003). ApoA-IV genotype was not related to change in total cholesterol, LDL-C or triglyceride concentrations. Therefore, weight loss as a treatment to reduce CVD risk factors may be more effective in subjects with the apoA-IV-1/1 variant as compared to those with the apoA-IV-1/2 variant, especially in subjects with type 2 diabetes.     

The N363S polymorphism in the glucocorticoid receptor gene is associated with overweight in subjects with type 2 diabetes mellitus

OBJECTIVE: A single nucleotide polymorphism (A1220G; N363S) in exon 2 of the glucocorticoid receptor gene (NR3C1), associated with increased sensitivity to glucocorticoids, was shown to be associated with obesity in nondiabetic subjects. Here, we investigated the impact of this variant on traits related to obesity and hyperglycaemia in subjects with type 2 diabetes mellitus. PATIENTS AND MEASUREMENTS: The N363S variant was screened by restriction fragment length polymorphism technique following DNA amplification by polymerase chain reaction in 369 French Caucasians with type 2 diabetes mellitus. RESULTS: Twenty subjects were found to be heterozygous for the variant (AG genotype frequency 0.0542). The prevalence of overweight [body mass index (BMI) > 25 kg/m2] was higher in AG carriers than in AA carriers (100%vs. 73%, P = 0.003). Moreover, the mean body weight and the BMI were higher in AG as compared to AA carriers, although only the body weight was significantly different between groups. However, when only the men were considered, a significantly higher BMI was observed in AG as compared to AA carriers: 30.0 +/- 4.8 vs. 27.3 +/- 4.6 kg/m2 (BMI Z-score 1.28 +/- 1.38 vs. 0.55 +/- 1.17; P = 0.035). No evidence was found for an association of the N363S variant with parameters related to the severity of hyperglycaemia. CONCLUSIONS: The 363S allele of the N363S variant of NR3C1 is associated with the susceptibility to overweight in subjects with type 2 diabetes mellitus.     

Mutations in the adiponectin gene in lean and obese subjects from the Swedish obese subjects cohort

Adiponectin (also called AdipoQ, gelatin-binding protein 28, Acrp30) DNA sequence variants were determined in 96 unrelated female subjects with severe obesity (mean body mass index [BMI], 42.3 kg/m2) and in 96 non-obese female controls (mean BMI, 23.0 kg/m2) from the Swedish Obese Subjects (SOS) cohort. A single base substitution (T45G) at codon 15 of exon 2 resulting in no change in amino acid (Gly15Gly) was found in equal frequencies among obese and control subjects. However, this polymorphism was associated with serum cholesterol and waist circumference (P=.023 and.043, respectively) in the obese group. A IVS2 + G62T sequence variation was also identified, but had similar prevalence rates in obese and control subjects. Blood glucose was highest in the obese female subjects who were homozygotes for the G allele (GG) of the IVS2 + G62T polymorphism (N=56; P=.033) and all the diabetics (n=6) in this sample were in this group. IVS2 + G62T polymorphism was also associated with BMI (P=.014), diastolic blood pressure (P=.009), and sagittal diameter (P=.032). A missense point mutation at codon 111 (Tyr111His) was not associated with any obesity-related phenotypes. In conclusion, adiponectin DNA sequence variations might play a role in the complications of morbid obesity and should be further investigated.     

Functional effect of the p22phox -930A/G polymorphism on p22phox expression and NADPH oxidase activity in hypertension

Oxidative stress induced by superoxide is implicated in hypertension. NADPH oxidase is the main source of superoxide in phagocytic and vascular cells, and the p22phox subunit is involved in NADPH oxidase activation. Recently we reported an association of -930A/G polymorphism in the human p22phox gene promoter with hypertension. This study was designed to investigate the functional role of this polymorphism in hypertension. We thus investigated the relationships between the -930A/G polymorphism and p22phox expression and NADPH oxidase-mediated superoxide production in phagocytic cells from 70 patients with essential hypertension and 70 normotensive controls. Genotyping of the polymorphism was performed by restriction fragment length polymorphism. NADPH oxidase activity was determined by chemiluminescence assays, and p22phox mRNA and protein expression was measured by Northern and Western blotting, respectively. Compared with hypertensive subjects with the AA/AG genotype, hypertensive subjects with the GG genotype exhibited increased (P<0.05) phagocytic p22phox mRNA (1.26+/-0.06 arbitrary unit [AU] versus 0.99+/-0.03 AU) and protein levels (0.58+/-0.05 AU versus 0.34+/-0.04 AU) and enhanced NADPH oxidase activity (1998+/-181 counts/s versus 1322+/-112 counts/s). No differences in these parameters were observed among genotypes in normotensive cells. Transfection experiments on vascular smooth muscle cells showed that the A-to-G substitution of this polymorphism produced an increased reporter gene expression in hypertensive cells. Nitric oxide production, as assessed by measurement of serum nitric oxide metabolites, was lower in GG hypertensive subjects than in AA/AG hypertensive subjects. In conclusion, these results suggest that hypertensive subjects carrying the GG genotype of the p22phox -930A/G polymorphism are highly exposed to NADPH oxidase-mediated oxidative stress.     

冠心病患者HSP70-2+1267A/G多态性与高敏C反应蛋白水平的相关性研究

冠心病（coronary artery disease,CAD）的病理基础是动脉粥样硬化,炎症是动脉粥样硬化的特征之一;研究发现炎症在冠状动脉粥样硬化斑块的发生、发展和粥样斑块的破裂过程中起重要作用,动脉粥样硬化被认为是一种慢性炎症的过程。热休克蛋白70-2（Hot Shock Protein,HSP）是HSP家族中重要的一员,