Influence of beta(2)-adrenoceptor gene polymorphisms on diet-induced thermogenesis

The sympathetic nervous system is involved in the control of energy metabolism and expenditure. Diet-induced thermogenesis is mediated partly by the ss-adrenergic component of this system. The aim of the present study was to investigate the role of genetic variation in the beta(2)-adrenoceptor in diet-induced thermogenesis. Data from twenty-four subjects (fourteen men and ten women; BMI 26.7(sem 0.8) kg/m(2); age 45.2(sem1.4) years) with different polymorphisms of the beta(2)-adrenoceptor at codon 16 (Gly16Gly, Gly16Arg or Arg16Arg) were recruited for this study. Subjects were given a high-carbohydrate liquid meal, and the energy expenditure, respiratory exchange ratio, and plasma concentrations of NEFA, glycerol, glucose, insulin and catecholamines were measured before and over 4 h after the meal. The AUC of energy expenditure (diet-induced thermogenesis) was not significantly different between polymorphism groups, nor was the response of any of the other measured variables to the meal. In a multiple regression model, the only variable that explained a significant proportion (32 %) of the variation in diet-induced thermogenesis was the increase in plasma adrenaline in response to the meal (P<0.05). The beta(2)-adrenoceptor codon16 polymorphisms did not contribute significantly. In conclusion, an independent contribution of the codon 16 polymorphism of the beta(2)-adrenoceptor gene to the variation in thermogenic response to a high-carbohydrate meal could not be demonstrated. The interindividual variation in thermogenic response to the meal was correlated with variations in the plasma adrenaline response to the meal.     

The association between violence victimisation and common symptoms in Swedish women

STUDY OBJECTIVE: To investigate the association between violence and abuse suffered by women during childhood or adult life, and the manifestation of a high level of common physical and mental symptoms. DESIGN, SETTING AND PARTICIPANTS: A questionnaire was sent to a random population of women, 40 to 50 years of age, living in a rural Swedish community. The response rate was 81.7 per cent (397 women). Odds ratios were used to estimate bivariate associations between the experience of violence/abuse and common symptoms. Multiple logistic regression analyses were used to test for confounding and effect modification. MAIN RESULTS: The experience of violence or abuse during childhood was reported by 32.2 per cent of the women, while 15.6 per cent reported being abused as an adult. In both cases, these experiences reached statistical significance in their association with a high level of common symptoms (OR=1.67; 95% CI 1. 08, 2.49 and OR=2.26; 95%CI 1.30, 3.92, respectively). The associations between childhood and as well adult experience of violence or abuse and common symptoms were largely independent of potential confounders such as unemployment, job strain, social support, and sense of coherence. The combined exposure to adult violence/abuse and low psychosocial coping resources, such as low social support or a low level of sense of coherence, considerably increased the odds ratio for common symptoms and a synergistic effect seemed to exist. CONCLUSION: Violence or abuse experience is an important factor when considering illness manifestations in terms of common symptoms in women 40 to 50 years of age.     

Obesity risk is associated with carbohydrate intake in women carrying the Gln27Glu beta2-adrenoceptor polymorphism

Interindividual differences in the response to dietary intake are, in some cases, genotype dependent. Moreover, genotype-environment interactions may appear when the impact of lifestyle factors (e.g., diet) on a phenotype (e.g., BMI > 30 kg/m(2)) differs by genotype. A case-control study (obese subjects vs. normal weight controls) was conducted to assess a possible effect modification on obesity risk of the Gln27Glu polymorphism for the beta(2)-adrenoceptor gene depending on dietary intake. The sample included 159 subjects with BMI > 30 kg/m(2) and 154 controls with BMI < 25 kg/m(2). The allele frequency for the Glu27 polymorphism, as assessed by the polymerase chain reaction-restriction fragment length polymorphism methodology, was 0.40 in cases (obese) and 0.37 in controls (lean), which was similar to that of other Caucasian populations. The dietary intake was estimated by using a previously validated food frequency questionnaire. Obesity incidence was not directly affected by the polymorphism [odds ratio (OR) = 1.40; P = 0.246]. However, a significant interaction (effect modification) between carbohydrate (CHO) intake and the presence of the Glu27 variant in the probability of obesity was apparent. Thus, females with the polymorphism and a higher CHO intake [>49% energy (E)] had a higher obesity risk (OR = 2.56, P = 0.051). The product-term introduced in the logistic model to assess effect modification revealed a marginally significant interaction (P = 0.058) between both factors. Furthermore, a high intake of CHO (E > 49%) was associated with higher insulin levels among women carrying the Gln27Glu polymorphism (P < 0.01). This gene-nutrient interaction emphasizes the importance of examining the outcome of some obesity-related mutations depending on lifestyle (including diet) and may explain the heterogeneity of findings from previous studies.     

Diet, obesity and obesogenic trends in two generations of Swedish women

Objective  Secular trends in obesity and related lifestyle factors are reported in two generations of 38- and 50-year old Swedish women. Specifically, we describe changes in obesity and fat patterning, while examining concurrent shifts in factors that are proposed to be causally related to the modern obesity epidemic. Methods  A total of 1,270 women aged 38 or 50 were selected from population registries and examined in 1968/69 (born 1930 or 1918) or 2004/05 (born 1966 or 1954). Anthropometric methods and lifestyle questions were unchanged between earlier and later surveys. Dietary comparisons were based on 24-h recall, with additional questions about usual alcohol and salt consumption patterns. In subgroups, 24-h urinary sodium was determined. Results  Weight, height, waist circumference, waist-hip ratio, triceps and subscapular skinfold measures were all significantly higher in later-born cohorts, although BMI and obesity were not significantly changed. Higher sodium excretion was observed among later-born sub-groups, consistent with reports of increasing salt preference. Lower proportions of energy as fat and sucrose, but higher carbohydrate, protein and fiber concentrations were reported by later-born cohorts. There were shifts towards increased frequency of wine and liquor consumption, but decreased beer. Leisure time physical activity and perceived stress levels both increased significantly over 36 years. Conclusions  A number of anthropometric and lifestyle differences between two generations of Swedish women were observed. Increases in subcutaneous and abdominal fatness were detected without significantly increasing BMI. While some aspects of diet showed improvement, increases in salt preference and sodium excretion are cause for concern.     

Gln27Glu variant of Beta2-adrenoceptor gene affects male type fat accumulation in women

Background  

The β₂-adrenergic receptor (BAR2) is the main lipolytic receptor in white human adipose tissue. There is a functional glutamine 27 glutamic acid (Gln27Glu, rs 1042714) polymorphism in its gene, which has been variably associated with body mass index. This gene variant may be associated with male-type adiposity in women and thus increased cardiovascular risk. We investigated whether the BAR2 Gln27Glu polymorphism is associated with visceral fat and coronary intima thickness in women.     

Gender-specific association of a perilipin gene haplotype with obesity risk in a white population

OBJECTIVE: Perilipin is a class of protein-coating lipid droplets in adipocytes and steroidogenic cells. Our purpose was to examine the association between common single-nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus and obesity, as well as related phenotypes, in unrelated American adults. RESEARCH METHODS AND PROCEDURES: Four PLIN SNPs (PLIN 6209T>C, 11482G>A, 13041A>G, and 14995A>T) were typed in 734 white subjects (373 men and 361 women) attending a residential lifestyle intervention program. The baseline anthropometric and biochemical measures were used. Obesity was defined as BMI > or = 30 kg/m(2). RESULTS: Multivariate analysis demonstrated that, in women, two of the SNPs (13041A>G, and 14995A>T) were significantly associated with percentage body fat (p = 0.016 for 13041A>G and p = 0.010 for 14995A>T) and waist circumference (p = 0.020 for 13041A>G and p = 0.045 for 14995A>T). Moreover, haplotype analysis using these two SNPs indicated that haplotypes A/T and G/T were both associated with significantly increased obesity risk (odds ratio = 1.76, 95% confidence interval 1.07 to 2.90 for haplotype A/T, and odds ratio = 1.73, 95% confidence interval 1.06 to 2.82 for haplotype G/T) when compared with haplotype A/A. No significant associations between PLIN variations and obesity were found in men. DISCUSSION: Our data support the hypothesis that the PLIN locus may be a significant genetic determinant for obesity risk in whites and that women are more sensitive to the genetic effects of perilipin than men.     

Trends in body mass index and prevalence of obesity in Swedish women 1980-89.

STUDY OBJECTIVE--To assess changes in the body mass index (BMI, weight (kg)/height2 (m2)) and in the prevalence of obesity in Swedish women during the 1980s. DESIGN--Data from two successive cross sectional surveys were used. SETTING--The whole of Sweden. SUBJECTS--A total of 7419 women from a 1980-81 survey (response rate 84.6%) and 6306 women from a 1988-89 survey (response rate 80.3%), aged 16-84 years, and forming a representative sample of Swedish women. MEASUREMENTS AND MAIN RESULTS--The results were based on self reported weight and height during interview. The mean BMI of the whole population, adjusted for age, education level, socioeconomic group, region, and nationality, increased by 0.17 kg/m2 (p = 0.0056) over the eight year period. The increase was particularly pronounced in the group aged 25-34 years (0.74 kg/m2; p < 0.0001, which corresponds to more than 2 kg for a woman 168 cm tall). The higher mean BMI was also reflected in the relative increase in the prevalence of obesity (BMI > 28.6 kg/m2) by 19% (odds ratio (OR) = 1.19; 95% confidence interval (CI): 1.04, 1.37) and of the combination of overweight and obesity (BMI > 23.8 kg/m2) by 12% (OR = 1.12; 95% CI 1.03, 1.23) in the whole female population. CONCLUSIONS--During the 1980s the mean BMI and the prevalence of overweight and obesity in adult Swedish women increased. An influence of the sociocultural environment on the body weight in women was stronger than that in men.     

Depression in unemployed Swedish women

Two groups of Swedish women--51 employed and 96 unemployed--were compared in terms of their scores on the Beck Depression Inventory (BDI). It was hypothesized that unemployed women would be more depressed than their employed counterparts and further that the distress of unemployment would be reflected in elevations in cortisol values among those who were out of work. It was found, even when controlling for social support, stressful life events and marital status, that depression as seen in the BDI scores, was greater in the unemployed group. However, no relationship was observed between either cortisol and employment status or cortisol and depression.     

A recombinant DNA vaccine protects mice deficient in the alpha/beta interferon receptor against lethal challenge with Usutu virus

Usutu virus (USUV) is a mosquito-borne flavivirus whose circulation had been confined to Africa since it was first detected in 1959. However, in the last decade USUV has emerged in Europe causing episodes of avian mortality and sporadic severe neuroinvasive infections in humans. Remarkably, adult laboratory mice exhibit limited susceptibility to USUV infection, which has impaired the analysis of the immune responses, thus complicating the evaluation of virus–host interactions and of vaccine candidates against this pathogen. In this work, we showed that mice deficient in the alpha/beta interferon receptor (IFNAR (−/−) mice) were highly susceptible to USUV infection and provided a lethal challenge model for vaccine testing. To validate this infection model, a plasmid DNA vaccine candidate encoding the precursor of membrane (prM) and envelope (E) proteins of USUV was engineered. Transfection of cultured cells with this plasmid resulted in expression of USUV antigens and the assembly and secretion of small virus-like particles also known as recombinant subviral particles (RSPs). A single intramuscular immunization with this plasmid was sufficient to elicit a significant level of protection against challenge with USUV in IFNAR (−/−) mice. The characterization of the humoral response induced revealed that DNA vaccination primed anti-USUV antibodies, including neutralizing antibodies. Overall, these results probe the suitability of IFNAR (−/−) mice as an amenable small animal model for the study of USUV host virus interactions and vaccine testing, as well as the feasibility of DNA-based vaccine strategies for the control of this pathogen.     

Abdominal obesity and hyperglycemia mask the effect of a common APOC3 haplotype on the risk of myocardial infarction

BACKGROUND: Plasma apolipoprotein (apo) C-III strongly predicts myocardial infarction (MI) and directly activates atherogenic processes in vascular cells. Genetic variation in the insulin response element of the APOC3 promoter is associated with an increased risk of MI. OBJECTIVE: The objective was to determine whether the APOC3 promoter variation affects plasma apo C-III concentrations and MI only when insulin sensitivity is normal. DESIGN: The APOC3*222 haplotype, defined by the minor alleles of the single nucleotide polymorphisms 3238C-->G, -455T-->C, and -482C-->T, was studied in 1703 matched nonfatal case-control pairs with MI in the Central Valley of Costa Rica. We used fasting hyperglycemia and abdominal obesity as surrogates for insulin sensitivity. RESULTS: The APOC3*222 haplotype was associated with higher apo C-III concentrations only in those with the lowest waist circumference or fasting glucose concentration. The association between the APOC3*222 haplotype and nonfatal MI, previously reported in this population, was strongly influenced by fasting hyperglycemia and abdominal obesity. The odds ratios for MI for the APOC3*222 haplotype were 1.72 (95% CI: 1.16, 2.54) and 1.84 (1.31, 2.59) in subjects in the lowest quintiles of abdominal obesity and fasting hyperglycemia, respectively, and were 0.75 (0.54, 1.05) and 1.16 (0.85, 1.59) in subjects in the highest quintiles, respectively (P for interaction <0.05). CONCLUSION: The results support the concept that mutations in the APOC3 promoter inhibit the down-regulation of APOC3 expression by insulin. This cardioprotective system becomes dysfunctional in abdominal obesity and hyperglycemia.     

Violence against women by their intimate partner and common mental disorders

The World Health Organization considers gender violence a cause of anxiety, depression and suicidal thoughts among women. This study investigated the association between violence committed against women by their intimate partners, defined by psychologically, physically and sexually abusive acts, and common mental disorders, assessed by using the Self Reporting Questionnaire (SRQ-20). A population-based household survey was carried out among women aged 15–49 years in two sites: São Paulo, the largest Brazilian city, and Zona da Mata of Pernambuco, a region with both urban and rural areas in the Northeast of the country. A large proportion of women reported violence (50.7%). The most frequent forms were psychological violence alone (18.8%) or accompanied by physical violence (16.0%). The prevalence of mental disorders was 49.0% among women who reported any type of violence and 19.6% among those who did not report violence (p < 0.0001). After adjustment for demographic and socioeconomic characteristics, the nature of the relationship, stressful life events and social support, all the forms of violence studied, with the exception of sexual violence alone or accompanied by either physical or psychological violence (p = 0.09), were significantly associated with mental disorders: physical violence alone (OR 1.91; CI 95% 1.2–3.0), psychological violence alone (OR 2.00; CI 95% 1.5–2.6), sexual violence alone or accompanied by either physical or psychological violence (OR 1.80; CI 95% 0.9–3.6), both psychological and physical violence (OR 2.56; CI 95% 1.9–3.5) and all three forms of violence (OR 2.68; CI 95% 1.8–4.0).This is the first population-based study on the association between intimate partner violence and mental health in Brazil. It contributes to the existing body of research and confirms that violence, frequently experienced by women in the country, is associated with mental disorders. Policies and strategies aimed at reducing gender-based violence are necessary for preventing and reducing anxiety and depression among women.     

A parenteral DNA vaccine protects against pneumonic plague

The chemokine, lymphotactin (LTN), was tested as a molecular adjuvant using bicistronic DNA vaccines encoding the protective Yersinia capsular (F1) antigen and virulence antigen (V-Ag) as a F1-V fusion protein. The LTN-encoding F1-V or V-Ag vaccines were given by the intranasal (i.n.) or intramuscular (i.m.) routes, and although serum IgG and mucosal IgA antibodies (Abs) were induced, F1-Ag boosts were required for robust anti-F1-Ag Abs. Optimal efficacy against pneumonic plague was obtained in mice i.m.-, not i.n.-immunized with these DNA vaccines. These vaccines stimulated elevated Ag-specific Ab-forming cells and mixed Th cell responses, with Th17 cells markedly enhanced by i.m. immunization. These results show that LTN can be used as a molecular adjuvant to enhance protective immunity against plague.     

D2 dopamine receptor gene and obesity

The prevalence of Taql A D₂ dopamine receptor (DRD2) alleles was determined in 73 obese women and men. In this sample with a mean body mass index of 35.1, the A1 (minor) allele of the DRD2 gene was present in 45.2% of these nonalcohol, nondrug abusing subjects. The DRD2 A1 allele was not associated with a number of cardiovascular risk factors examined, including blood lipids (cholesterol, high-density lipoprotein [HDL]- and low-density lipoprotein [LDL]-cholesterol, and triglycerides). However, phenotypic factors characterized by the presence of parental history and postpuberty onset of obesity as well as carbohydrate preference were associated with obese subjects carrying the A1 allele. The cumulative number of these three factors was positively and significantly (p < .0002) related to A1 allelic prevalence. The data showing an association of the minor allele of the DRD2 gene with phenotypic characteristics suggest that this gene, located on q22–q23 region of chromosome 11, confers susceptibility to a subtype of this disorder. © 1994 by John Wiley & Sons, Inc.     

尾加压素Ⅱ基因多态性与2型糖尿病关系

目的 探讨尾加压素Ⅱ(UTS2)基因变异及其单倍型与2型糖尿病的关系.方法采用病例对照研究,应用聚合酶链式反应-限性性内切酶片段长度多态性(PCR-RFLP)技术,对UTS2基因多态性进行检测.结果 rs228648、rs2890565、rs228651的基因型在2组之间的分布差异有统计学意义(Prs228648＜0.001,Prs2890565=0.021,Prs228651=0.050).GACA单倍型在病例组中的频率(9.3%)显著低于对照组(20.3%,P=0.007),GGTG单倍型在病例组中的频率(4.0%)显著高于对照组(0.6%,P=0.015).标签基因(Tag SNPs)组成的单倍型GT和AT在病例组中的频率(分别为17.4%和11.1%)显著低于对照组(分别为22.6%和15.5%)(P均＜0.05).结果 rs228648(G/A)和rs228651(A/G)的位点变异与2型糖尿病的发生呈正关联,rs2890565(C/T)的TT基因型与2型糖尿病的发生成负关联.U152基因多态性及其单倍型与2型糖尿病的易感性有关.     

Virus-like particle-based vaccine against coxsackievirus A6 protects mice against lethal infections

Coxsackievirus A6 (CA6) is emerging as one of the major causative agents of hand, foot, and mouth disease (HFMD) worldwide. However, no vaccine is currently available for preventing CA6 infection. Here, we report the development of a virus-like particle (VLP)-based recombinant vaccine for CA6. We produced CA6 VLPs in insect cells by infecting the cells with a baculovirus coexpressing the genes encoding CA6 P1 and 3CD. Biochemical analyses showed that the produced VLPs consisted of VP0, VP1, and VP3 capsid subunit proteins generated by the cleavage of P1 by 3CD. Mice immunized with these VLPs produced CA6-specific serum antibodies. Passive transfer of antisera from CA6 VLP-immunized mice protected recipient mice from lethal infections caused by homologous and heterologous CA6 strains. Moreover, active immunization of mice with CA6 VLPs efficiently conferred protection against both homologous and heterologous CA6 infections. These results suggested that CA6 VLP-based recombinant vaccine is a promising candidate vaccine for preventing CA6 infection and can be incorporated into a multivalent HFMD vaccine formulation to achieve broad-spectrum and effective prevention of this disease.     

A single dose sub-unit vaccine protects against pneumonic plague

In this study, the protection afforded against aerosolised Yersinia pestis by injection of a single dose of an alhydrogel-adsorbed sub-unit vaccine has been compared with that given by an existing killed whole cell vaccine licensed for human use. The sub-unit vaccine, prepared by admixing F1 antigen derived from a Y. pestis cell culture supernatant with recombinant V antigen derived from an E. coli cell lysate, fully protected an outbred strain of mouse against exposure to 10(6) CFU of virulent plague organisms (10(4) mouse lethal doses, MLD). In contrast, the whole cell vaccine provided only 16% protection against the same level of challenge. Furthermore, sub-unit vaccinees were able to clear the bacteria from their lungs post-challenge whereas bacteria were cultured from the lungs of a surviving KWC vaccinee post-challenge. In killed whole cell vaccinees, physiologically significant levels of IgG to F1 only were detectable and the levels of F1-specific IgG in serum and in broncho-alveolar washings were significantly lower (p<0.05) compared with sub-unit vaccinees. In sub-unit vaccinees, an IgG titre to the F1 and V antigens was detected in serum where it was significantly higher (p<0.05) compared with broncho-alveolar washings suggesting that, at the time of challenge, protection is attributable mainly to the combined circulating IgG titre to the F1 and V sub-units. The enhanced protective efficacy of this sub-unit vaccine administered as a single dose compared with an existing vaccine has been demonstrated in an outbred animal model of pneumonic plague.     

Intestinal FABP2 A54T polymorphism: association with insulin resistance and obesity in women

OBJECTIVE: To assess the association between the Ala54Thr genetic polymorphism of the fatty acid-binding protein 2 (FABP2) gene with insulin resistance and obesity. RESEARCH METHODS AND PROCEDURES: According to a sampling scheme based on BMI, 33 adult obese women (BMI > or = 30) and 30 adult normal-weight women (BMI > 18.5 and < 25 kg/m(2)) were recruited for this study. Women with chronic inflammatory diseases or acute pathology were excluded. Glucose, insulin, leptin, lipids, and tumor necrosis factor alpha (TNF alpha) were measured in fasting plasma samples. Insulin resistance was estimated through the homeostasis model assessment for insulin resistance method. The Ala54Thr allelic variant was determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis. RESULTS: The Thr54 allele was more frequent in obese than in nonobese women (47.0% vs. 31.7; p = 0.08). Among obese women, higher TNF alpha concentrations were found when comparing the Thr54/Thr54 genotype (30.0 +/- 7.1 pg/mL) with either the Ala54/Thr54 genotype (21.2 +/- 8.4 pg/mL) or the Ala54/Ala44 genotype (20.1 +/- 7.0 pg/mL) (p < 0.05). In addition, higher fasting plasma insulin and leptin levels were found among Thr54/Thr54 homozygotes compared with the other genotypes (p < 0.05). DISCUSSION: Our results suggest that the Ala54Thr polymorphism of the FABP2 gene is associated with obesity and insulin resistance. The effect of this polymorphism might be mediated by elevated production of TNF alpha.     

The CYP19 gene and associations with androgens and abdominal obesity in premenopausal women

OBJECTIVE: Elevated androgens in women are associated with type 2 diabetes and are dependent on the conversion to estrogens by aromatase cytochrome P450. Polymorphisms of a tetranucleotide repeat [TTTA](n) in the fourth intron of the CYP19 gene are associated with endocrine-dependent diseases and were examined in relation to hormone levels and disease risk factors in premenopausal women. RESEARCH METHODS AND PROCEDURES: A population sample of women born in 1956 (n = 270) were genotyped for this polymorphism and the results set in relation to steroid hormones, including saliva cortisol, anthropometric variables, estimates of insulin, glucose and lipid metabolism, and blood pressure. RESULTS: Seven tetranucleotide repeat [TTTA](n) alleles were detected with allelic sizes of 168 to 195 bp, with a TCT deletion/insertion (168/171 bp) upstream of this microsatellite. Smoking was associated with elevated androgens (p = 0.005 to 0.019). Using the median (average stretch, 177.5 bp) as a dividing line, nonsmoking women with the shorter microsatellite had higher free testosterone (p = 0.018) and lower sex hormone binding globulin (p = 0.033). These differences were pronounced with the 168-bp allele. Such women were also characterized by a less-substantial decrease of morning cortisols ("unwinding"; p = 0.035) and central obesity (abdominal sagittal diameter, p = 0.049) and had waist/hip circumference ratios of borderline significance (p = 0.064). DISCUSSION: The results indicate that, in premenopausal women, a short microsatellite in the fourth intron of the CYP19 gene, caused by a TCT deletion upstream the [TTTA](n) tract, is associated with elevated androgens, perturbed regulation of the hypothalamic-pituitary-adrenal axis, and abdominal obesity.     

Neuromedin beta: a strong candidate gene linking eating behaviors and susceptibility to obesity

BACKGROUND: Obesity is frequently associated with eating disorders, and evidence indicates that both conditions are influenced by genetic factors. However, little is known about the genes influencing eating behaviors. OBJECTIVE: The objective was to identify genes associated with eating behaviors. DESIGN: Three eating behaviors were assessed in 660 adults from the Quebec Family Study with the use of the Three-Factor Eating Questionnaire. A genome-wide scan was conducted with a total of 471 genetic markers spanning the 22 autosomes to identify quantitative trait loci for eating behaviors. Body composition and macronutrient and energy intakes were also measured. RESULTS: Four quantitative trait loci were identified for disinhibition and susceptibility to hunger. Of these, the best evidence of linkage was found between a locus on chromosome 15q24-q25 and disinhibition (P <0.0058) and susceptibility to hunger (P <0.0001). After fine-mapping, the peak linkage was found between markers D15S206 and D15S201 surrounding the neuromedin beta (NMB) gene. A missense mutation (p.P73T) located within the NMB gene showed significant associations with eating behaviors and obesity phenotypes. The T73T homozygotes were 2 times as likely to exhibit high levels of disinhibition (odds ratio: 1.8; 95% CI: 1.07, 2.89; P=0.03) and susceptibility to hunger (odds ratio: 1.9; 95% CI: 1.15, 3.06; P=0.01) as were the P73 allele carriers. Six-year follow-up data showed that the amount of body fat gain over time in T73T subjects was >2 times that than in P73P homozygotes (3.6 compared with 1.5 kg; P <0.05). CONCLUSION: The results suggest that NMB is a very strong candidate gene of eating behaviors and predisposition to obesity.