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1.
Objective: To investigate AGT secretion in cultured adipocytes from obese patients and its relationship with obesity‐related phenotypes, blood pressure, and the M235T polymorphism in the AGT gene. Research Methods and Procedures: Measurements, including anthropometry, body composition (DXA), and blood pressure, were performed in 61 overweight or obese women (BMI: 28 to 68 kg/m2). A subcutaneous abdominal adipose tissue biopsy was used for adipocyte size determination and quantification of AGT secretion in the medium of cultured adipocytes. AGT M235T genotype was determined using polymerase chain reaction‐restriction fragment length polymorphism. Results: Adipose secretion of the AGT protein (range, 140 to 2575 ng/106 cells/24 h) was not significantly correlated with BMI, body fat, or blood pressure and did not vary according to the M235T polymorphism in the AGT gene. However, the AGT M235T polymorphism was associated with adipocyte size (111.6 ± 2.8, 108.8 ± 1.9, 118.2 ± 2.6 μm in MM, MT, and TT genotypes, respectively; p < 0.01) after adjustment for age and fat mass. An association between the AGT M235T polymorphism and adipocyte size (p < 0.02 adjusted for sex, age, and BMI) was found in another independent sample of 106 obese subjects (sex ratio, M/F 16/90; BMI, 29 to 70 kg/m2). Discussion: In cultured adipocytes from obese subjects, AGT secretion was not associated with body fat phenotypes, blood pressure, or fat cell size. However, results from two independent studies suggest an association between the AGT M235T polymorphism and adipocyte size.  相似文献   

2.
Allele and genotype frequencies of the T174M polymorphism of the angiotensinogen gene were for the first time estimated in the West Siberian population. The polymorphism was tested for association with coronary atherosclerosis (CAS) and with several quantitative risk factors in patients with angiographically verified CAS, healthy individuals, and in a population sample nondifferentiated with respect to CAS.  相似文献   

3.
Objectives : Markers of insulin resistance are often apparent in nondiabetic relatives of subjects with type 2 diabetes. Whether diabetes family history (FH) also predicts visceral fat accumulation and, if so, whether the increased insulin resistance in relatives of diabetic subjects occurs independently of visceral fat accumulation are not known. Research Methods and Procedures : To examine this issue, we studied the relationship of diabetes FH with insulin sensitivity and fat measures, measured by minimal model analysis and computed tomography, respectively, in families participating in the Insulin Resistance Atherosclerosis (IRAS) Family Study. FH scores were based on the diabetes status of the participants’ parents and older siblings. Results : FH scores were significantly correlated with reduced insulin sensitivity (p < 0.05) and increased subcutaneous (p < 0.05) and visceral (p < 0.05, San Antonio only) fat in families from San Antonio and Los Angeles but not in the leaner Hispanic families from San Luis Valley. There was no evidence for a stronger association of FH score with visceral fat accumulation than with subcutaneous fat or insulin resistance. Discussion : The absence of an association between FH score and insulin resistance/fat accumulation in San Luis Valley is consistent with the idea that the expression of transmitted diabetes genes may be suppressed in leaner, more physically active populations.  相似文献   

4.
Objective: The relationship among body fat distribution, blood pressure, serum leptin levels, and insulin resistance was investigated in hypertensive obese women with central distribution of fat. Research Methods and Procedures: We studied 74 hypertensive women (age, 49.8 ± 7.5 years; body mass index, 39.1 ± 5.5 kg/m2; waist-to-hip ratio, 0.96 ± 0.08). All patients were submitted to 24-hour blood pressure ambulatory monitoring (24h-ABPM). Abdominal ultrasonography was used to estimate the amount of visceral fat (VF). Fasting blood samples were obtained for serum leptin and insulin determinations. Insulin resistance was estimated by homeostasis model assessment insulin resistance index (HOMA-r index). Results: Sixty-four percent of the women were postmenopausal, and all patients showed central distribution of fat (waist-to-hip ratio > 0.85). The VF correlated with systolic 24h-ABPM values (r = 0.28, p = 0.01) and with HOMA-r index (r = 0.27; p = 0.01). VF measurement (7.5 ± 2.3 vs. 5.9 ± 2.2 cm, p < 0.001) and the systolic 24h-ABPM (133 ± 14.5 vs. 126 ± 9.8 mm Hg, p = 0.04), but not HOMA-r index, were significantly higher in the postmenopausal group (n = 48) than in the premenopausal group (n = 26). No correlations were observed between blood pressure levels and HOMA-r index, leptin, or insulin levels. In the multiple regression analysis, visceral fat, but not age, body fat mass, or HOMA-r index, correlated with the 24h-ABPM (p = 0.003). Discussion: In centrally obese hypertensive women, the accumulation of VF, more often after menopause, is associated with higher levels of blood pressure and insulin resistance. The mechanism through which VF contributes to higher blood pressure levels seems to be independent of leptin or insulin levels.  相似文献   

5.
A major gene hypothesis for resting metabolic rate (RMR) was investigated using segregation analysis (POINTER) of data on families participating in Phase 2 of the Québec Family Study. Complete analyses were conducted on RMR adjusted for age, and also on RMR adjusted for age and other covariates, primarily fat mass (FM) and fat-free mass (FFM). Prior to adjustment for covariates, support for a major gene hypothesis was equivocal — i.e., there was evidence for either a major gene or a multifactorial component (i.e., polygenic and/or familial environment). The multifactorial model was preferred over the major gene model, although the latter did segregate according to Mendelian expectations. However, after the effects of FM and FFM were accounted for, a major gene effect was unambiguous and compelling. The putative locus accounted for 57% of the variance, affected 7% of the sample, and led to high values of RMR. The lack of a significant multifactorial effect suggested that the familial etiology of RMR adjusted for FM and FFM was likely to be entirely a function of the major locus. Comparing the RMR results from pre- and post-adjustment for FM and FFM suggests a plausible hypothesis. We know from earlier studies in this sample that there is a putative major gene for FM and a major non-Mendelian effect for FFM. The current study leads us to speculate that: (1) the gene(s) affecting body size and body composition also may have an effect on RMR, and further (2) removal of the effect of the major gene(s) for body size and composition allowed for detection of an additional major gene affecting only the RMR. Thus, RMR appears to be an oligogenic trait.  相似文献   

6.
RICE, TREVA, JP DESPRÉS, LOUIS PÉRUSSE, JACQUES GAGNON, ARTHUR S LEON, JAMES S SKINNER, JACK H WILMORE, DC RAO, CLAUDE BOUCHARD. Segregation analysis of abdominal visceral fat: The HERITAGE Family Study. A major gene hypothesis for abdominal visceral fat (AVF) level, both before and after adjustment for total body fat mass, was investigated in 86 white families who participated in the HERITAGE Family Study. In this study, sedentary families were tested for a battery of measures (baseline), endurance exercise trained for 20 weeks, and then remeasured again. The baseline measures reported here are unique in that the variance due to a potentially important environmental factor (activity level) was limited. AVF area was assessed at L4 to L5 by the use of computerized tomography scan, and total body fat mass was assessed with underwater weighing. For fat mass, a putative locus accounted for 64% of the variance, but there was no evidence of a multifactorial component (i.e., no polygenic and/or common familial environmental effects). For AVF area, both a major gene effect accounting for 54% of the variance and a multifactorial component accounting for 17% of the variance were significant. However, after AVF area was adjusted for the effects of total level of body fat, the support for a major gene was reduced. In particular, there was a major effect for fat mass-adjusted AVF area, but it was not transmitted from parents to offspring (i.e., the three transmission probabilities were equal). The importance of this study is twofold. First, these results confirm a previous study that suggested that there is a putative major locus for AVF and for total body fat mass. Second, the findings from the HERITAGE Family Study suggest that the factors underlying AVF area in sedentary families may be similar to those in the population at large, which includes both sedentary and active families. Whether the gene(s) responsible for the high levels of AVF area is the same as that which influences total body fat content remains to be further investigated.  相似文献   

7.
Cardiovascular and metabolic parameters were evaluated in 15 female spayed dogs before and after they became obese on either a saturated fat (LD, lard, n=8) or unsaturated fat (CO, corn oil, n=7) diet. Body weight and body fat increased significantly in both groups, although no differences occurred between diet groups. Dogs receiving the LD diet exhibited a greater increase in mean arterial pressure than those receiving the CO diet (p<0. 01; 15. 9 ± 2. 1 vs. 9. 8 ± 3. 3 mm Hg increase). The CO diet stimulated a greater increase in heart rate than the LD diet (p<0. 05; 32. 8 ± 7. 8 vs. 14. 1 ± 5. 8 bpm increase). Ganglionic blockade with chlorisondamine caused an increase in HR in both lean groups and in the obese CO group, but not the obese LD group, consistent with a decrease in parasympathetic tone to the heart in the dogs overfed saturated fat. Obesity enhanced the heart rate response to β-badrenergic stimulation by isoproterenol in the LD, but not CO group. The LD diet increased circulating insulin and decreased insulin sensitivity, whereas the CO diet had no effect on either parameter. These findings suggest that the composition of dietary fat can modulate the autonomic and metabolic adaptations induced by dietary obesity.  相似文献   

8.
Objective: The role of leptin in the association between body mass, central adiposity, and blood pressure (BP) is controversial. This study evaluated the relationship between leptin and BP in relation to body mass index (BMI) and fat distribution in a large sample of untreated male adults. Research Methods and Procedures: The study population was made up of 457 untreated male employees of the Olivetti factory in Naples. Plasma leptin, complete anthropometry, BP, and relevant biochemical variables were measured. Results: Log‐transformed plasma leptin levels were directly associated with BMI (r = 0.661, p < 0.001) and waist circumference (r = 0.630; p < 0.001). Leptin also correlated with systolic (r = 0.258) and diastolic (r = 0.277) BP (p < 0.001). The association between leptin and BP was maintained after accounting for age, BMI (or waist circumference), log‐insulin, and serum creatinine (p < 0.01); this association was stronger than that with BMI. Logistic regression analysis showed that an increased prevalence of hypertension (BP ≥ 140 and/or 90 mm Hg) was associated with high plasma leptin levels when controlling for age and waist circumference (odds ratio, 1.99; 95%CI, 1.06 to 3.72) or for age and BMI (odds ratio, 1.92; 95%CI, 1.02 to 3.61). Discussion: A graded positive relationship between plasma leptin levels and BP was observed in this sample of untreated male adults. This association was independent of age, BMI, abdominal adiposity, and fasting plasma insulin. Moreover, elevated plasma leptin concentrations were associated with greater probability of hypertension, again independently of potential confounders.  相似文献   

9.
Objective: The aims were to determine if 1) individuals who became and maintained overweight during their entire lifetime differ from those who were never‐overweight in terms of annual changes in adiposity and concurrent changes in cardiovascular disease (CVD) risk factors; 2) the changes and their relationships to each other varied between these groups or by sex within the groups; and 3) alcohol usage, smoking habits, and level of physical activity differed between groups. Research Methods and Procedures: Data from 16,315 examinations of 414 individuals were utilized to assess lifetime overweight (body mass index [BMI] > 25 kg/m2) status. A regressive analytic approach was used to determine the average annual changes for each individual over an adult serial interval ranging from 4 to 20 years. Results: Men and women who have become and maintained overweight have higher blood pressure and a poorer lipid/lipoprotein risk profile than those who have never been overweight. There is an accelerated deterioration in the atherogenic profile of overweight men and women as indicated by annual changes in CVD risk factors about double that of their never‐overweight counterparts. In women, increased risk is derived from increasing systolic and diastolic blood pressure, whereas in men the increased risk comes not only from increasing diastolic blood pressure but also cholesterol, triglycerides, and low‐density lipoprotein cholesterol levels and, to a lesser extent, decreasing high‐density lipoprotein cholesterol. Discussion: The reduced physical activity observed in the overweight adults may be related to their accumulation of adipose tissue at a rate about double their never‐overweight counterparts, and this may be driving the higher rate of increase of CVD risk factors in the overweight groups.  相似文献   

10.
Objective: To evaluate whether subclinical hypothyroidism (SH) affects resting energy expenditure (REE) as well as body composition, lipid profile, and serum leptin in obese patients. Research Methods and Procedures: A total of 108 obese patients with SH defined as normal free thyroxine levels and thyroid‐stimulating hormone (TSH) values of >4.38 μU/ml (mean ± 2 SD of the values of our reference group of obese patients with normal thyroid function) were compared with a group of 131 obese patients matched for age, sex, and body mass index (BMI) but with normal TSH levels. We assessed estimated daily caloric intake by 7‐day recall, REE by indirect calorimetry, body composition by bioelectrical impedance analysis, serum leptin by radioimmunoassay, and lipid profile (i.e., total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, and triglycerides). Results: All of the variables measured were not different between the euthyroid obese patients and those with SH. In a multiple regression model with REE expressed for kilograms of fat free mass (REE/kgFFM) as a dependent variable and percentage of fat mass, BMI, waist‐to‐hip ratio, age, TSH, free thyroxine, serum leptin, and caloric intake as independent variables, only percentage of fat mass was significantly correlated with REE/kgFFM in both groups. In the SH group only, BMI, waist‐to‐hip ratio, age, and TSH were related to REE/kgFFM and explained 69.5% of its variability. After dividing the patients with SH using a cutoff TSH value of 5.7 μU/ml, which represents 3 SD above the mean of TSH levels of the group of obese patients with normal thyroid function, only REE/kgFFM was significantly different and lower in the group of more severely hypothyroid patients. Discussion: In patients with obesity, SH affects energy expenditure only when TSH is clearly above the normal range; it does not change body composition and lipid profile. We suggest that, at least in obese patients, evaluation of TSH levels may be useful to rule out a possible impairment of resting energy expenditure due to a reduced peripheral effect of thyroid hormones.  相似文献   

11.
The alleles and genotypes of the T174M polymorphism of the angiotensinogen gene were PCR-analyzed in Russians and Tatars from Bashkortostan. The genotype frequency distribution observed in either ethnic group did not differ from that reported for other populations. The T174M polymorphism was tested for association with essential hypertension (EH). Genotypes TT, TM, and MM were found respectively in 82.56, 13.95, and 3.49% normotensive Russians and in 83.81, 16.19, and 0% normotensive Tatars. The frequency of genotype TM in patients with EH onset beyond 45 years of age was significantly higher than in controls of the same age without signs of cardiovascular disorders (51.72 vs. 11.11% in Russians and 45.45 vs. 16% in Tatars). Patients with EH onset under 45 did not differ in genotype frequency distribution from normotensive subjects of the same age. Genotype TM was associated with higher risk of EH in people over 45.  相似文献   

12.
Several large epidemiological studies have shown an association between body mass index and blood pressure in normal weight and overweight patients. Weight gain in adult life especially seems to be an important risk factor for the development of hypertension. Weight loss has been recommended for the obese hypertensive patient and has been shown to be the most effective nonpharmacological treatment approach. However, long‐term results of weight loss programs are disappointing with people often regaining most of the weight initially lost. In recent years, a modest weight loss, defined as a weight loss of 5% to 10% of baseline weight, has received increasing attention as a new treatment strategy for overweight and obese patients. A more gradual and moderate weight loss is more likely to be maintained over a longer period of time. Several studies have confirmed the blood pressure‐lowering effect of a modest weight loss in both hypertensive and nonhypertensive patients. A modest weight loss can normalize blood pressure levels even without reaching ideal weight. In patients taking antihypertensive medication, a modest weight loss has been shown to lower or even discontinue the need for antihypertensive medication. In patients with high normal blood pressure, a modest weight loss can prevent the onset of frank hypertension. The blood pressure‐lowering effect of weight loss is most likely a result of an improvement in insulin sensitivity and a decrease in sympathetic nervous system activity and occurs independent of salt restriction. In conclusion, a modest weight loss that can be maintained over a longer period of time is a valuable treatment goal in hypertensive patients.  相似文献   

13.
Objective: Investigate the familial aggregation of amount and distribution of subcutaneous fat and their changes in response to endurance training. Research Methods and Procedures: A total of 483 sedentary subjects from 99 nuclear families were recruited, trained for 20 weeks of exercising on cycle ergometers, and measured before and after training for the following indicators of subcutaneous fat and fat distribution: trunk fat (TRUNK = sum of abdominal, subscapular, suprailiac, and midaxillary skinfolds), extremity fat (EXTREM = sum of biceps, triceps, thigh, and calf skinfolds), subcutaneous fat (SF8 = sum of the eight skinfolds), the trunk to extremity skinfolds ratio adjusted for SF8 (TER) and waist girth adjusted for body mass index (WAIST). The familial aggregation of the age‐ and sex‐adjusted baseline phenotypes and their responses to training (Δ) after adjustment for the baseline values was investigated using a familial correlation model. Results: Significant familial aggregation was observed for all the phenotypes measured at baseline and for ΔTRUNK and ΔWAIST. Transmissibility estimates reached about 30% to 35% for TRUNK, EXTREM, and SF8 and 50% for TER and WAIST. The transmissibilities of the response phenotypes were lower, ranging from 0% for ΔWAIST to 21% for ΔTRUNK and the pattern of familial correlations suggested a greater within‐ than between‐generation resemblance in the response. Discussion: This study suggests that the amount and distribution of subcutaneous fat strongly aggregates in families, whereas the response to exercise training is characterized by a moderate and more complex pattern of familial resemblance. We conclude that familial/genetic factors are more important in determining the amount and distribution of subcutaneous fat than their responses to exercise training.  相似文献   

14.
The latest data (NHANES III) from the National Center for Health Statistics (NCHS) show that the black population has the highest proportion of overweight among all adult populations in the United States. The present study compared the body mass index (BMI) and body fat percent from dual-photon absorptiometry in 1,324 healthy adults aged 18 to 107 years recruited from four ethnic groups in the New York City area; 523 whites, 280 blacks, 267 Asians and 254 Puerto Ricans. Puerto Ricans had the largest BMI and the largest percent of subjects with body weight more than 120% of their ideal weight, and the largest fat percent of the four ethnic groups: 76% of Puerto Rican males had fat percent above the median value for white males (fat percent = 19.6%) and 95% of Puerto Rican females had fat percent above the median for white females (fat percent = 30.8%). Asians had the smallest BMI, but 63% of them had fat percent above the median values for whites in each gender. Puerto Ricans also had the largest waist-to-hip ratios among the four ethnic groups. In blacks, the percent of subjects with fat percent larger than the median for whites was slightly smaller than that for Puerto Ricans, 64% and 82% of males and females respectively. These results differ from the latest NCHS data and show that Puerto Ricans in this sample are heavier and fatter than blacks.  相似文献   

15.
Associations of parity with body fat and its distribution are poorly understood; therefore, we examined the relationships between parity and obesity in young adult women. Body mass index (BMI), skin folds, and waist-hip ratio were compared in 1452 African-American and 1268 Caucasian nonpregnant women aged 18 to 30, adjusting for age (where no age-parity interactions were present), education, physical activity (assessed by questionnaire) and fitness (assessed by graded exercise test), dietary fat intake, alcohol and smoking. Adjusted mean BMI was significantly higher in African-American women aged 25–30 years with three or more children (28.5 kg/m2) than in those with two (27.0 kg/m2), one (26.2 kg/m2), or no children (26.3 kg/m2). Similar trends were found in Caucasians (BMI = 23.3, 23.4, 23.7, 25.0 kg/m2 for parity = 0,1, 2, ≥ 3, respectively), but the mean BMI was significantly higher in African Americans in each parity group. The association between BMI and parity was not present among women 18–24 years of age. Skinfolds were directly associated with parity in African Americans only. Waist-hip ratios were generally lower among nulliparous than parous women in both ethnic groups; race differences were present only among nulliparas. In conclusion, parity was associated with BMI in women aged 25 to 30 years but did not explain ethnicity-related differences in body mass.  相似文献   

16.
17.
The aim of the present project was to investigate whether repeated visits by a therapy dog to nursing homes might affect the older residents’ systolic blood pressure and heart rate. A secondary aim was to investigate and compare effects (differences in responses) in older people with high and normal systolic blood pressure. The project consisted of two consecutive studies; the dog study (two researchers and a therapy dog with a handler visited the residents at three nursing homes, n = 13), and the control study (the two researchers alone visited the residents at three different nursing homes, n = 13). The studies were divided into three periods; period 1 (weeks 1–2), period 2 (weeks 3–4), and period 3 (weeks 5–6) and included two visits per week. The dog and her handler visited during periods 2 and 3 in the dog study. Participants’ heart rate and blood pressure were measured at 0 and 20 minutes at each visit. The data were analyzed using Friedman's two- way analysis of Variance by Rank with post-hoc analysis using Wilcoxon signed-rank tests with a Bonferroni correction, and also with the Mann-Whitney U test for independent samples. In the dog study, participants’ heart rate decreased significantly (p = 0.006) from period 1 to period 3. Participants with an initial systolic blood pressure ≥ 130 mmHg had a significant decrease in both systolic blood pressure (p = 0.009) and heart rate (p = 0.009). In the control study, participants’ heart rate and systolic blood pressure did not change significantly. The participants in the dog study had a significantly lower systolic blood pressure during period 3 (p = 0.016) compared with those in the control study. In conclusion, repeated visits by a therapy dog–handler team decreased the older adults’ heart rate, and for those with high initial systolic blood pressure, blood pressure also decreased. In addition, systolic blood pressure decreased significantly in the dog group when compared with the control group.  相似文献   

18.
Objective: To examine whether there is a major gene effect on fasting insulin and pleiotropic loci for fasting insulin, total fat mass (FM), and abdominal visceral fat (AVF). Research Methods and Procedures: A major gene hypothesis for fasting plasma insulin levels was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of white descent who participated in the HERITAGE Family Study. Results: Segregation analyses were performed on insulin adjusted for age, on insulin adjusted for age and FM, and on insulin adjusted for age and AVF. Before adjustment for AVF and FM, a major gene effect on fasting insulin levels was indicated. The putative locus accounted for 54% of the variance under a recessive inheritance pattern, affecting 11% of the sample (i.e., allele frequency = 0.33). However, after adjusting for the effects of AVF or FM, neither a major effect alone nor a multifactorial component alone could be rejected, and support for a major gene was equivocal, i.e., neither the hypothesis of Mendelian τ values or that of the equal τs were rejected and the equal τ model fit the data better than the Mendelian τ model. This pattern (i.e., major gene evidence for insulin before but not after adjustment for AVF or FM) suggests that there is a putative locus with pleiotropic effects on both insulin and FM and another pleiotropic locus for both insulin and AVF. Discussion: Although these data do not directly support an additional major gene for insulin independent of AVF and FM, such support cannot be ruled out because there is still a significant major effect on FM‐ or AVF‐adjusted insulin (albeit the Mendelian nature of this effect is ambiguous).  相似文献   

19.
Objective: To investigate the association between the Trp64Arg polymorphism of the β3‐adrenergic receptor gene and changes in body composition in response to endurance training. Research Methods and Procedures: Adult sedentary white and black subjects participating in the HERITAGE Family Study were measured before and after 20 weeks on endurance training for the body mass index, fat mass, percentage of body fat, fat‐free mass, sum of eight skinfolds, and subcutaneous, visceral, and total abdominal fat areas. The association between the Trp64Arg polymorphism and the response phenotypes, computed as the difference between pre‐ and post‐training values, was tested by analysis of covariance separately in men and women. The gene by race interaction term was also tested. Results: No race differences were observed for allelic and genotype frequencies. Training resulted in significant reduction of body fat in both men and women. No association of the Trp64Arg polymorphism was observed with training‐induced changes for any of the body composition phenotypes in both men and women. Discussion: These results suggest that the Trp64Arg polymorphism of the β3‐adrenergic receptor gene is not related to changes in body composition in response to exercise training.  相似文献   

20.
In the present investigation, we have attempted to identify regions of the genome in which “obesity genes” potentially reside using robust sib-pair linkage analysis. Data were collected on 1,628 individuals in 301 nuclear families residing in the environs of Québec City during the period 1978–1981. In addition to traditional blood group antigens and enzyme polymorphisms, several phenotypes in the obesity domain that are associated with increased morbidity were assessed, including measures relating to heaviness (i.e., the body mass index), body composition and nutrient partitioning (i.e., % body fat), and regional fat distribution without and with standardization for total fat mass (i.e., the sum of six skinfold thicknesses, and the ratio of the sums of trunk to extremity skinfold thicknesses). Three consistent patterns of potential linkage relationships with obesity phenotypes were revealed in these data, involving the marker loci adenosine deaminase, the Kell blood group antigen, and esterase D, which identify chromosomal regions 20q13, 7q33, and 13q14, respectively. Other potential linkages also were identified in the short arm of chromosome 1, interesting because of the presence of the db and fa loci on homologous regions of chromosome 1 in mouse and rat models of obesity, respectively. Each of the tentative linkage relationships reported here warrant follow-up using alternative methods and require replication in independent studies.  相似文献   

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