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S M Echwald

Publications and source records attributed to S M Echwald.

At least 19 recordsLinked to original sources
PubMed2002

Association studies between microsatellite markers within the gene encoding human 11beta-hydroxysteroid dehydrogenase type 1 and body mass index, waist to hip ratio, and glucocorticoid metabolism.

Two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert active cortisol (F) and inactive cortisone (E). 11beta-HSD1 is an oxo-reductase (E to F) expressed in several glucocorticoid target tissues, including liver and adipose tissue, where it facilitates glucocorticoid-induced gluconeogenesis and adipocyte differentiation, respectively. We have isolated a full-length HSD11B1 genomic clone; the gene is more than 30 kb in length, not 9 kb in length as previously reported, principally due to a large intron 4. Two polymorphic (CA)(n) repeats have been characterized within intron 4: a CA(19) repeat 2.7 kb 3' of exon 4 and a CA(15) repeat 3 kb 5' of exon 5. The microsatellites, CA(19) and CA(15), were PCR amplified using fluorescent primers and were genotyped on an ABI 377 DNA sequencer from DNA of 413 normal individuals enrolled in the MONICA study of cardiovascular risk factors and 557 Danish men (ADIGEN study), of whom 234 were obese [body mass index (BMI), >/=31 kg/m(2) ] at draft board examination and 323 were randomly selected controls from the draftee population with BMI below 31 kg/m(2) (mean +/- SE, 21.7 +/- 0.41). Genotypic data from the normal MONICA cohort was compared with gender, 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio, and waist to hip (W:H) ratio. When analyzed by allele length (0, 1, or 2 short alleles) for the CA(19) marker, there was a trend toward a higher 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio (P = 0.058) and an increased W:H ratio (2 vs. 0.1 short; P(c) = 0.10) with overrepresentation of short alleles. The opposite was true for the CA(15) locus, with longer alleles at this locus predicting increased 11beta-HSD1 activity, particularly in females. Genotypic data from the ADIGEN case-control population was compared with clinical markers of obesity such as BMI and W:H ratio. There was no significant difference in the distribution of either microsatellite marker between lean and obese groups. Allele distributions were binomial, as seen for the MONICA cohort, and the data were split accordingly (zero, one, or two short alleles). No significant association was seen between grouped alleles and the clinical parameters. No association was observed between HSD11B1 genotype and BMI in either population. These data suggest that 11beta-HSD1 is not a major factor in explaining genetic susceptibility to obesity per se. However, weak associations between HSD11B1 genotype, increased 11beta-HSD1 activity, and W:H ratio suggest that polymorphic variability at the HSD11B1 locus may influence susceptibility to central obesity through enhanced 11beta-HSD1 activity (E to F conversion) in visceral adipose tissue.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2001

Obesity genes.

Explore the source record for details and available documents.

Environment↗
PubMed2001

Genetic variability of the SUR1 promoter in relation to beta-cell function and Type II diabetes mellitus.

AIMS/HYPOTHESIS: We aimed to examine the promoter of SUR1 for genetic variation and to determine if variants were associated with Type II (non-insulin-dependent) diabetes mellitus or measures of beta-cell function. METHODS: We examined 465 bp upstream of the ATG site in 46 Type II diabetic patients and 15 glucose tolerant control subjects by SSCP-heteroduplex analysis. RESULTS: We identified an a --> t substitution 437 bp upstream of the ATG site. The allelic frequency was similar in 455 unrelated Type II diabetic patients and in 203 glucose tolerant control subjects matched for age (0.036, [95 % CI 0.019-0.053] vs 0.034 [95 % CI 0.009-0.059]; p = 0.92). Among the glucose tolerant subjects there were no differences between non-carriers (n = 189) and carriers (n = 14) of the variant in fasting values or 30 min values of plasma glucose and serum insulin during an oral glucose tolerance test. In a study of 233 glucose tolerant offspring of and spouses to Danish Caucasian Type II diabetic patients, non-carriers (n = 193) and carriers (n = 37) of the -437 a/t polymorphism did not differ in glucose or tolbutamide stimulated insulin response during an intravenous glucose tolerance test with intravenous tolbutamide injection [AUCs-insulin (0-8) min, 2290 +/- 1660 vs 2308 +/- 1935 pmol/l x min and AUCs-insulin(20-30 min), 3113 +/- 2033 vs. 3393 +/- 2830 pmol/l x min, respectively]. CONCLUSION/INTERPRETATION: We have identified a novel a/t polymorphism of the SUR1 gene promoter which is not associated with Type II diabetes mellitus or measures of beta-cell function. Previous reported non-functional variants of SUR1 associated with Type II diabetes mellitus still need to be accounted for.

ATP-Binding Cassette Transporters↗
PubMed2001

The Asn363Ser variant of the glucocorticoid receptor gene is not associated with obesity or weight gain in Danish men.

OBJECTIVE: Testing association of the Asn363Ser variant of the glucocorticoid gene with measures of obesity and weight gain. SUBJECTS: 741 obese subjects (BMI > or = 31 kg/m(2) at selection) and 854 random control subjects from the same population, examined at draft board examination and after on average 27.4+/- y. A lean control group (n=351) was further selected as the fraction from the cohort group having a BMI below 25.0 kg/m(2) at the latest examination. METHODS: Using PCR-RFLP subjects were genotyped for the Asn363Ser variant and grouped according to genotype. RESULTS: The prevalence of the Ser363 allele was 4.7% (95% Cl: 3.3-6.2%) among the obese, 4.1% (2.7-5.5%) among the random cohort subjects and 4.3% (2.1-6.5%) among lean control subjects, respectively, showing no significant differences between the groups (P > 0.1). Furthermore, no differences in BMI, waist-hip ratio or weight gain were seen within any of the groups when defined according to the glucocorticoid receptor genotype. CONCLUSION: In the examined population this marker is not a relevant predictor of obesity.

Adult↗
PubMed2000

Studies of the variability of the genes encoding the insulin-like growth factor I receptor and its ligand in relation to type 2 diabetes mellitus.

Insulin-like growth factor I (IGF-I) is an important regulator of many aspects of growth, differentiation, and development, and as low birth weight has been associated with impaired glucose tolerance and overt type 2 diabetes in adult life, we considered the genes encoding the IGF-I and the IGF-I receptor (IGF-IR) as candidates for low birth weight, insulin resistance, and type 2 diabetes. Here we report the mutational analysis of the coding regions of the IGF-I and IGF-IR performed on genomic DNA from probands of 82 Danish type 2 diabetic families. No mutations predicting changes in the amino acid sequences of the IGF-I or IGF-IR genes were detected, but several silent and intronic polymorphisms were found. The impact of the most prevalent polymorphism, GAG1013GAA of the IGF-IR, was evaluated in a population-based sample of 349 young healthy subjects, where the variant had an allele frequency of 0.44 (95% confidence interval, 0.40-0.48). No significant relationships between this variant and birth weight, birth length, or insulin sensitivity index were detected. In addition, we did not observe any significant differences in allelic frequencies of the codon 1013 variant between 395 type 2 diabetic patients (allele frequency, 0.52; 95% confidence interval, 0.49-0.55) and 238 matched glucose-tolerant control subjects (allelic frequency, 0.47; 95% confidence interval, 0.43-0.50). In conclusion, variability in the coding regions of IGF-I and the IGF-IR does not associate with reduced birth weight, insulin sensitivity index, or type 2 diabetes in the Danish population.

Adult↗
PubMed2000

The K121Q variant of the human PC-1 gene is not associated with insulin resistance or type 2 diabetes among Danish Caucasians.

The human plasma-cell membrane differentiation antigen-1 (PC-1) has been shown to inhibit insulin receptor tyrosine kinase activity. Recently, a K121Q polymorphism in the human PC-1 gene was found in a Sicilian population and was shown to be strongly associated with insulin resistance. The objectives of the present investigation were to examine in the Danish Caucasian population whether the K121Q variant was associated with type 2 diabetes or, in glucose-tolerant subjects, with impaired whole-body insulin sensitivity. We genotyped 404 Danish type 2 diabetic patients and found that the allele frequency of the variant was 0.14 (95% CI 0.12-0.16), whereas the allele frequency was 0.16 (95% CI 0.13-0.19) among 237 matched glucose-tolerant control subjects (P = 0.6). In the control subjects, there were no significant differences among wild-type, heterozygous, or homozygous subjects in regard to 1) serum insulin and plasma glucose levels at fasting, 60 min, or 120 min during an oral glucose tolerance test (OGTT) or 2) the estimates of insulin resistance obtained from the homeostasis model assessment (HOMA). Furthermore, we investigated the impact of the variant in 2 other Danish population samples that comprised 356 young healthy subjects and 226 glucose-tolerant offspring of type 2 diabetic probands, respectively. In all of the study populations, the polymorphism was not associated with an altered insulin sensitivity index as estimated from an intravenous glucose tolerance test in combination with an intravenous injection of tolbutamide. In addition, among the 226 offspring, the variations in serum insulin and serum C-peptide responses measured during an OGTT were not related to the PC-1 genotype. In conclusion, the K121Q polymorphism of the human PC-1 gene is not associated with type 2 diabetes or insulin resistance among Danish Caucasians.

Adult↗
PubMed1999

Sequence variants in the human cocaine and amphetamine-regulated transcript (CART) gene in subjects with early onset obesity.

OBJECTIVE: The cocaine and amphetamine-regulated transcript (CART) is expressed in the brain of rodents and humans, and intracerebroventricular injection of the peptide in rats reduces food intake. The objective of the present study was to chromosomally map the CART gene and to examine the coding region of the gene for variability in obese subjects. METHODS: The coding region of the CART gene was analyzed by single-strand conformation polymorphism analysis in 84 subjects with early onset obesity. The prevalence of identified mutations was estimated in a cohort of 757 subjects with juvenile onset obesity [body mass index (BMI) = 35.7+/-5.7 kg/m2+/-standard deviation (S)] and in 890 random control subjects (BMI = 26.1+/-3.6 kg/m2+/-S). Furthermore, using radiation hybrid mapping we mapped the chromosomal localization of the human CART gene. RESULTS: Radiation hybrid mapping co-localized the CART gene with a recently published human obesity locus at chromosome 5q13-14 corresponding also to an obesity locus at the similar syntenic region in mice. We identified two silent polymorphisms in the 3'UTR region of the gene (position 1457 deletion of A and position 1475 A-->G substitution) and the prevalence of these was determined among obese and control subjects. However, none of the variants were associated with either obesity or weight gain during an average follow-up period of 27.4+/-8.4 years (S). CONCLUSION: Mutations in the coding region of the CART gene are unlikely to be involved in body weight control in Danish Caucasians with early onset obesity.

Adolescent↗
PubMed1999

Mutational analysis of the proopiomelanocortin gene in Caucasians with early onset obesity.

OBJECTIVE: Mutations in the human gene encoding the polyhormone peptide proopiomelanocortin (POMC) are associated with obesity in rare cases and the gene co-localizes with a reported quantitative trait loci (QTL) for variations in circulating leptin levels and fat mass on human chromosome 2p21. In this study we have used polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) analysis, to test whether variations in the human POMC gene are associated with human obesity. DESIGN AND SUBJECTS: Primary mutational analysis was performed on the coding region of the POMC gene and 500 bp of the putative promoter region, by single strand conformational analysis and sequencing, in 56 subjects with juvenile onset obesity (body mass index (BMI) > or = 31 kg/m2 at the draft board examination). The prevalence of two polymorphisms were further studied in 156 obese and 205 control subjects, and in a population based cohort of 380 extensively characterized young healthy subjects. RESULTS: We have identified a total of six gene variants, five were silent nucleotide substitutions (No51(promoter) g-->c, No670(5'UTR)g-->a, No4512(codon6)c-->t Cys/Cys, No7726(codon116)c-->t Leu/Leu) of which one was prevalent (No8246(3'UTR)c-->t) and one variant changed an amino acid (No8086(codon236)g-->c Arg/Gln). The amino acid substitution was only seen in one subject. Comparing the prevalence of the frequent No8246 silent polymorphism, in an association study comprising 156 subjects with juvenile onset obesity and 205 randomly sampled control subjects (mean BMI 23.5+/-4.7 kg/m2), did not show any relationship to obesity. Also, comparing the prevalence of a known 9bp insertion/deletion variant in the coding region of the gene between obese and lean, showed no association to obesity. Furthermore, analyzing a population based cohort of 380 young healthy Caucasians for the prevalent 3'UTR polymorphism as well as the 9 bp insertion/deletion variant did not show any association to deviations in body fat contents or fasting serum leptin concentrations. CONCLUSION: In conclusion, it is unlikely that variations in the coding region and the putative promoter of the POMC gene are a major cause of juvenile onset human obesity.

3' Untranslated Regions↗
PubMed1999

Genetics of human obesity: lessons from mouse models and candidate genes.

Obesity is a common disorder with potentially serious negative implications on health and quality of life and a rising prevalence worldwide, warranting effective treatments. The disorder runs in families, and important knowledge is expected to follow the identification of human obesity genes. Although statistical analysis of inheritance of obesity in humans suggests a large genetic component in obesity, up to 80%, few actual obesity genes have been identified so far. However, a number of obesity causing genes have successfully been cloned from rodents with monogenic forms of obesity, and it is probable that new knowledge in the field of human obesity will result from these findings.

Animals↗
PubMed1999

Analysis of the relationship between fasting serum leptin levels and estimates of beta-cell function and insulin sensitivity in a population sample of 380 healthy young Caucasians.

OBJECTIVE: Circulating leptin levels correlate positively with the degree of obesity and prolonged hyperinsulinaemia increases serum leptin levels. Moreover, insulin secreting beta-cells express functional leptin receptors indicating a functional relationship between leptin and insulin. The aim of this study was to examine the relationship between fasting serum leptin levels and measures of insulin sensitivity and beta-cell function in a population-based sample of 380 young healthy Caucasians. DESIGN AND METHODS: Multiple regression analysis was employed to analyse the relationship between fasting serum leptin levels and levels of fasting serum insulin, insulin sensitivity index and acute insulin response (AIR) in a population-based study of 380 young healthy Caucasians who underwent a combined intravenous glucose and tolbutamide tolerance test. RESULTS AND CONCLUSION: Serum leptin levels were positively correlated to measures of adiposity and were 3.2 times higher in women than in men (P<0.00001). In multiple regression analyses adjusting for age, percentage body fat, waist circumference and maximal aerobic capacity, a significant positive correlation was observed between the fasting serum leptin concentrations and both fasting serum insulin levels (P<0.0001) and AIR (P = 0.014) for women. No significant interrelation of these variables was found in men. However, for both genders a significant negative correlation was observed between fasting serum leptin levels and measures of insulin sensitivity index (P = 0.007).

Adolescent↗
PubMed1999

Mutational analysis of the coding regions of the genes encoding protein kinase B-alpha and -beta, phosphoinositide-dependent protein kinase-1, phosphatase targeting to glycogen, protein phosphatase inhibitor-1, and glycogenin: lessons from a search for genetic variability of the insulin-stimulated glycogen synthesis pathway of skeletal muscle in NIDDM patients.

The finding of a reduced insulin-stimulated glucose uptake and glycogen synthesis in the skeletal muscle of glucose-tolerant first-degree relatives of patients with NIDDM, as well as in cultured fibroblasts and skeletal muscle cells isolated from NIDDM patients, has been interpreted as evidence for a genetic involvement in the disease. The mode of inheritance of the common forms of NIDDM is as yet unclear, but the prevailing hypothesis supports a polygenic model. In the present study, we tested the hypothesis that the putative inheritable defects of insulin-stimulated muscle glycogen synthesis might be caused by genetic variability in the genes encoding proteins shown by biochemical evidence to be involved in insulin-stimulated glycogen synthesis in skeletal muscle. In 70 insulin-resistant Danish NIDDM patients, mutational analysis by reverse transcription-polymerase chain reaction-single strand conformation polymorphism-heteroduplex analysis was performed on genomic DNA or skeletal muscle-derived cDNAs encoding glycogenin, protein phosphatase inhibitor-1, phophatase targeting to glycogen, protein kinase B-alpha and -beta, and the phosphoinositide-dependent protein kinase-1. Although a number of silent variants were identified in some of the examined genes, we found no evidence for the hypothesis that the defective insulin-stimulated glycogen synthesis in skeletal muscle in NIDDM is caused by structural changes in the genes encoding the known components of the insulin-sensitive glycogen synthesis pathway of skeletal muscle.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed1998

Organisation of the coding exons and mutational screening of the uncoupling protein 3 gene in subjects with juvenile-onset obesity.

Uncoupling proteins (UCPs) are mitochondrial transporters that uncouple the cellular respiration releasing stored energy as heat. Recently a third member of the UCP family was identified. Human UCP3 is different from UCP1 and UCP2 by its high and preferential expression in skeletal muscle and consequently the UCP3 gene is an attractive candidate gene for obesity. In this study we have determined the intron/exon organization of the coding region of the UCP3 gene and performed single strand conformation polymorphism (SSCP) analysis and direct sequencing of variants of the gene in 60 Caucasian subjects with juvenile-onset obesity. We detected 4 nucleotide substitutions in the intron regions and 2 silent amino acid variants. During the identification of the intron/exon structure of the gene in a normal healthy male subject with a BMI of 23.5 kg/m2, a nucleotide substitution replacing a glycine with a serine was identified at codon84. This variant was neither found among 156 subjects with juvenile-onset obesity nor among 205 control subjects. In a population based sample of 380 young healthy subjects the Gly/Ser84 variant was found in one female subject with a BMI of 25.5 kg/m2 and a fat mass of 23.7 kg. We conclude it is unlikely that variants in the coding region of the UCP3 gene contribute to the pathogenesis of juvenile-onset obesity among Danish Caucasians.

Adolescent↗
PubMed1998

Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell responses and functional expression studies in Chinese hamster fibroblast cells.

The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are insulinotropic factors released from the small intestine to the blood stream in response to oral glucose ingestion. The insulinotropic effect of GLP-1 is maintained in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas, for unknown reasons, the effect of GIP is diminished or lacking. We defined the exon-intron boundaries of the human GIP receptor, made a mutational analysis of the gene and identified two amino acid substitutions, A207 V and E354Q. In an association study of 227 Caucasian Type II diabetic patients and 224 matched glucose tolerant control subjects, the allelic frequency of the A207 V polymorphism was 1.1% in Type II diabetic patients and 0.7% in control subjects (p = 0.48), whereas the allelic frequency of the codon 354 polymorphism was 24.9% in Type II diabetic patients versus 23.2% in control subjects. Interestingly, the glucose tolerant subjects (6% of the population) who were homozygous for the codon 354 variant had on average a 14% decrease in fasting serum C-peptide concentration (p = 0.01) and an 11% decrease in the same variable 30 min after an oral glucose load (p = 0.03) compared with subjects with the wild-type receptor. Investigation of the function of the two GIP receptor variants in Chinese hamster fibroblasts showed, however, that the GIP-induced cAMP formation and the binding of GIP to cells expressing the variant receptors were not different from the findings in cells expressing the wildtype GIP receptor. In conclusion, amino acid variants in the GIP receptor are not associated with random Type II diabetes in patients of Danish Caucasian origin or with altered GIP binding and GIP-induced cAMP production when stably transfected in Chinese hamster fibroblasts. The finding of an association between homozygosity for the codon 354 variant and reduced fasting and post oral glucose tolerance test (OGTT) serum C-peptide concentrations, however, calls for further investigations and could suggest that GIP even in the fasting state regulates the beta-cell secretory response.

Alleles↗
PubMed1998

Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene.

The high-affinity sulfonylurea receptor (SUR1) is, as a subunit of the ATP-sensitive potassium channel, an important regulator of insulin secretion in the pancreatic beta-cell. The aim of this study was to examine if genetic variability of the SUR1 gene was associated with NIDDM or altered pancreatic beta-cell function. Mutational analysis of all the 39 SUR1 exons, including intron-exon boundaries, in 63 NIDDM patients revealed two missense variants, five silent variants in the coding region, and four intron variants. The two missense variants (Asp673Asn and Ser1369Ala) and two sequence variants (ACC-->ACT, Thr759Thr and a c-->t intron variant in position -3 of the exon 16 splice acceptor site) were examined for association with NIDDM and for a possible influence on insulin and C-peptide secretion after intravenous glucose and tolbutamide loads in a random sample of unrelated, healthy, young Danish Caucasians. The Asp673Asn variant in exon 14 was only identified in one NIDDM patient, and the allelic frequency of the Ser1369Ala was similar among 247 control subjects (0.38 [95% CI 0.34-0.42]) and 406 NIDDM patients (0.40 [0.37-0.43]). The allelic frequency of the silent exon 18 Thr775Thr variant was 0.051 (0.035-0.067) in NIDDM patients (n=392) and 0.027 (0.013-0.041) in control subjects (n=246; chi2=4.99, P=0.03). The allelic frequency of the intron variant was similar among NIDDM patients (0.45 [0.42-0.48]) and control subjects (0.44 [0.40-0.48]). Of 386 NIDDM patients, 17 had the combined genotype exon 18 C/T and intron -3c/-3t (0.044 [0.024-0.064]), whereas 3 of 243 control subjects had the same combined genotype (0.012 [0-0.026]; chi2=4.87, P=0.03; odds ratio: 3.69 [1.07-12.71]). Of 380 unrelated, healthy, young Danish Caucasians, 10 (0.026 [0.010-0.042]) had the combined at-risk genotype. These subjects had, on average, a 50% reduction in serum C-peptide and a 40% reduction in serum insulin responses upon tolbutamide injection (P=0.002 and P=0.05, respectively) but normal serum C-peptide and insulin responses upon glucose injection. In conclusion, a silent polymorphism in exon 18 of the SUR1 gene is associated with NIDDM in a Danish Caucasian population. In combination with an intron variant, the association is higher, and young, healthy carriers of the intragenic combination have reduced serum C-peptide and insulin responses to a tolbutamide load.

ATP-Binding Cassette Transporters↗
PubMed1997

Amino acid variants in the human leptin receptor: lack of association to juvenile onset obesity.

The recently described putative lipostat system mediated in part by leptin and its hypothalamic receptor provides logical candidate genes for the molecular basis of inherited obesity in humans on the basis of the occurrence of profound obesity observed in obese and diabetic mice, in which the genes for leptin or its receptor, respectively, are mutated. In this study we tested the hypothesis that juvenile onset obesity in humans may be caused by leptin resistance mediated through genetic variations in isoforms of the hypothalamic leptin receptor. One hundred and fifty-six obese Danish men with a history of juvenile onset obesity were selected at the draft board examination with a body mass index (BMI) > or = 31 kg/m2. From the same study population a control group of 205 control subjects (mean BMI = 21,5 kg/m2) were randomly selected. Single strand conformational polymorphism scanning of genomic DNA from 56 obese subjects revealed a total of four amino acid variants located in coding exons 2, (Lys109Arg), 4 (Lys204Arg and Gln223Arg), and 12 (Lys656Asn), respectively. The codons 109, 223, and 656 variants were common, but their prevalence was not significantly different between obese and lean carriers with regard to allele or carrier frequency (p > 0.1 in each case). The codon 204 mutation was only found in one obese subject. In conclusion, it is unlikely that mutations in the coding region of the long isoform of the leptin receptor are a common cause of juvenile onset obesity.

Adolescent↗
PubMed1997

Identification of two novel missense mutations in the human OB gene.

OBJECTIVE: To clone the human OB gene and to investigate if mutations in the OB gene are related to juvenile onset obesity in Caucasians. DESIGN: Case-cohort study with mutational scanning of the OB gene in an obese cohort and in a population sample of young Caucasians. SUBJECTS: An obese cohort of 156 subjects with juvenile onset obesity and a population sample of 380 healthy young Caucasians. MEASUREMENTS: Various anthropometric and biochemical measures of obesity and insulin sensitivity and single strand conformation polymorphism scanning and nucleotide sequencing. RESULTS: Analysis of the coding region of the OB gene in the 536 participants revealed that one obese subject was heterozygous for a mutation at codon Phe17Leu and one normal weight subject was heterozygous for a mutation at codon Val110Met. The phenotypes of the carriers were not different from matched non-mutation carrying subjects. CONCLUSIONS: Mutations exist in the OB gene among obese as well as lean subjects although they are rare. However, it is unlikely that mutations in the coding region of the OB gene are a common cause of juvenile onset obesity among Caucasians.

Adult↗