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T Hansen

Publications and source records attributed to T Hansen.

At least 145 records · Page 8Linked to original sources
PubMed1999

Strand displacement amplification and homogeneous real-time detection incorporated in a second-generation DNA probe system, BDProbeTecET.

BACKGROUND: Amplified DNA probes provide powerful tools for the detection of infectious diseases, cancer, and genetic diseases. Commercially available amplification systems suffer from low throughput and require decontamination schemes, significant hands-on time, and specially trained laboratory staff. Our objective was to develop a DNA probe system to overcome these limitations. METHODS: We developed a DNA probe system, the BDProbeTecTMET, based on simultaneous strand displacement amplification and real-time fluorescence detection. The system uses sealed microwells to minimize the release of amplicons to the environment. To avoid the need for specially trained labor, the system uses a simple workflow with predispensed reagent devices; a programmable, expandable-spacing pipettor; and the 96-microwell format. Amplification and detection time was 1 h, with potential throughput up to 564 patient results per shift. We tested 122 total patient specimens obtained from a family practice clinic with the BD ProbeTecET and the Abbott LCx(R) amplified system for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: Based on reportable results, the BDProbeTecET results for both organisms were 100% sensitive and 100% specific relative to the LCx. CONCLUSIONS: The BDProbeTecET is an easy-to-use, high-throughput, closed amplification system for the detection of nucleic acid from C. trachomatis and N. gonorrhoeae and other organisms.

Chlamydia trachomatis↗
PubMed1998

Common amino acid substitutions in insulin receptor substrate-4 are not associated with Type II diabetes mellitus or insulin resistance.

The family of insulin receptor substrates (IRS1-4) is defined by proteins with an overall similar structure. IRS-1 and IRS-2 have been shown to have key roles in cellular transmission of the action of insulin, insulin-like growth factor-1 and various cytokines. We have previously identified amino acid polymorphisms in the human IRS-1 and IRS-2 proteins. Given the documented importance of IRS-1 and -2 in insulin signalling and the implications of distribution of these genes for the pathogenesis of insulin resistance and diabetes, we decided that the most recently identified member of the IRS family, IRS-4, was a relevant candidate to examine for genetic variability which might be associated with subsets of diabetes or insulin resistance. The gene encoding IRS-4 was analysed by the single strand conformation polymorphism technique in 83 Danish Caucasians with Type II (non-insulin-dependent) diabetes mellitus. Five amino acid polymorphisms were identified: Leu34Phe, Arg411Gly, Gly584Cys, His879Asp and Lys883Thr. In an association study of 324 patients with Type II diabetes and 267 control subjects with normal glucose tolerance the polymorphism at codon 34 was found with allelic frequencies of 3.9 and 2.3 %, respectively, the variant at codon 411 with allelic frequencies of 3.9 and 5.6%, respectively, and the variant at codon 879 with frequencies of 19.2 and 18.0%, respectively. Each carrier of the codon 34 polymorphism was also a carrier of the codon 411 and codon 879 variants and similarly, carriers of the variant at codon 411 were also carriers of the polymorphism at codon 879. The variants at codon 584 and 883 were each found in only one Type II diabetic patient. The allelic frequencies of the variants at codon 411 and 879 were also determined in 380 young healthy subjects (4.6 and 18.1 %, respectively). The insulin sensitivity index as estimated by Bergman's minimal model of the young healthy subjects carrying either polymorphism was indistinguishable from the carriers of wild-type IRS-4. Moreover, none of the men were heterozygous for the IRS-4 polymorphisms indicating that the gene is located on the X-chromosome. In conclusion, amino acid polymorphisms in human IRS-4 are common in Caucasians but are not associated with Type II diabetes or with insulin resistance in young healthy subjects.

Adaptor Proteins, Signal Transducing↗
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

Mutations in the hepatocyte nuclear factor-1alpha gene in Caucasian families originally classified as having Type I diabetes.

Mutations in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene are the cause of maturity-onset diabetes of the young type 3 (MODY3), which is characterised by a severe impairment of insulin secretion and an early onset of the disease. Also at onset of diabetes some MODY patients show similar clinical symptoms and signs as patients with Type I (insulin-dependent) diabetes mellitus. The objective of this study was to estimate the prevalence of MODY3 patients misclassified as Type I diabetic patients. From a large population-based sample of unrelated Danish Caucasian Type I diabetic patients with an affected first degree relative, 39 patients (6.7%) who did not carry any high-risk HLA-haplotypes, i.e. DR3 or DR4 or both were examined by single-strand conformational polymorphism scanning and direct sequencing of the coding region and the minimal promoter of the HNF-1alpha gene. Four of the 39 Type I diabetic patients (10%) were identified as carrying mutations in the HNF-1alpha gene. One patient carried a missense mutation (Glu48Lys) in exon 1, two patients carried a missense mutation (Cys241Gly) in exon 4 and one patient carried a frameshift mutation (Pro291fsdelA) in exon 4. The mutations were all identified in heterozygous form, segregated with diabetes, and were not identified in 84 unrelated, healthy subjects. Furthermore, family history in three of the four families showed diabetes in four consecutive generations, suggestive of an autosomal dominant inheritance. In conclusion, about 10% of Danish diabetic patients without a high-risk HLA-haplotype, originally classified as having Type I diabetes could have diabetes caused by mutations in the HNF-1alpha gene. Clinical awareness of family history of diabetes and mode of inheritance might help to identify and reclassify these diabetic subjects as MODY3 patients.

Adolescent↗
PubMed1998

Ligand-free MHC class I conformation.

Perhaps the most important structural questions regarding MHC molecules concern what changes occur when the MHC molecule binds peptide. Extensive new biochemical evidence indicates that peptide-empty MHC class I molecules adapt an unstable and partially folded conformation.

Animals↗
PubMed1998

Puncture technique and postural postdural puncture headache. A randomised, double-blind study comparing transverse and parallel puncture.

BACKGROUND: This clinical study was conducted in order to investigate the effect of two different orientations of the bevel during dural puncture on development of postural postdural puncture headache (PPDPH). METHODS: Two hundred and eighteen patients aged 18 to 50 years scheduled for minor non-obstetric surgery using spinal anaesthesia (SA) were included in this randomised, double-blind study. Dural puncture was performed using a 0.42 mm O.D. (27-g) Quincke spinal needle with the orientation of the bevel parallel or transverse relative to the longitudinal axis of the dural cylinder. All patients were blinded with regard to the puncture technique, and so was the anaesthesiologist performing a telephone interview 5 to 7 days postoperatively. The occurrence and duration of headache, backache and other complaints were recorded. Headache was classified as PPDPH or non-PPDPH, and intensity of the headache was registered using a numerical rating scale (NRS) from 0 to 10. RESULTS: Two hundred and twelve patients with a mean age of 35.3 years completed the study, 106 in each group. The two groups were comparable with regard to mean age, sex, local anaesthetics used and surgical procedure performed. Headache occurred in 44 patients postoperatively. PPDPH was diagnosed in 4/106 patients (3.8%) in the parallel group and 24/106 (22.6%) in the transverse group (P < 0.0002). Postoperative backache occurred in 31 and 20 patients (parallel compared to transverse) (NS). CONCLUSIONS: Dural puncture with the bevel of the needle transverse to the longitudinal axis of the dural cylinder gave significantly more cases of PPDPH than puncture with the bevel parallel to this axis even when using a 27-g Quincke needle. When using Quincke bevelled needles care must be taken to assure that the orientation of the bevel is parallel to the longitudinal axis of the dural sac.

Adolescent↗
PubMed1998

The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1alpha gene on estimates of the pancreatic beta-cell function in Caucasian glucose-tolerant first-degree relatives of type 2 diabetic patients.

The objective of the present study was to investigate whether the frequent amino acid polymorphisms, Ile/Leu27 and Ser/Asn487, of the hepatocyte nuclear factor-1alpha gene were associated with alterations in glucose-induced serum C-peptide and serum insulin responses among glucose-tolerant first-degree relatives of type 2 diabetic patients. The study comprised 2 independent Danish cohorts. Among 74 unrelated type 2 diabetic relatives, 12 homozygous carriers of the Ile/Leu27 polymorphism had a 32% decrease in the 30-min serum C-peptide level (P = 0.01), as well as a 39% decrease in the 30-min serum insulin level (P = 0.02) during an oral glucose tolerance test. Ten homozygous carriers of the Ile/Leu27 variant did, however, not differ from wild-type carriers, with respect to the acute circulating insulin and serum C-peptide responses during an i.v. glucose tolerance test in the same study cohort. In a larger (more than 3-fold) study group of 230 glucose tolerant offspring of 62 type 2 diabetic probands, 33 homozygous carriers of the Ile/Leu27 variant did not differ, with respect to either serum insulin and serum C-peptide levels during an oral glucose tolerance test or acute serum insulin and serum C-peptide responses during an i.v. glucose tolerance test. We therefore consider the former positive finding as a statistical type I error. There were no differences in the above mentioned variables between carriers of the Ser/Asn487 polymorphism and wild-type carriers within any of the 2 study populations. Nor did carriers of combined genotypes, i.e. carriers of both the Ile/Leu27 and the Ser/Asn487 variants, show any associations with the examined variables. In conclusion, the Ile/Leu27 and Ser/ Asn487 polymorphisms of the hepatocyte nuclear factor-1alpha gene have apparently no major impact on the pancreatic beta-cell function, after an oral and i.v. glucose challenge, in Caucasian first-degree relatives of type 2 diabetic patients.

Adult↗
PubMed1998

The Ala/Val98 polymorphism of the hepatocyte nuclear factor-1alpha gene contributes to the interindividual variation in serum C-peptide response during an oral glucose tolerance test: evidence from studies of 231 glucose-tolerant first degree relatives of type 2 diabetic probands.

The third form of maturity-onset diabetes of the young is caused by mutations in the hepatocyte nuclear factor-1alpha gene. Recently, we demonstrated an association between a prevalent polymorphism at codon 98, Ala/Val98, of this gene and a 20% decreased insulin release during an oral glucose tolerance test (OGTT) in middle-aged glucose-tolerant Danish Caucasian subjects. The major objective of the present study was to replicate this finding among glucose-tolerant first degree relatives of type 2 diabetic patients of the same ethnic origin. All participants, 231 glucose-tolerant offspring of 62 type 2 diabetic probands, underwent an OGTT with measurements of plasma glucose, serum insulin, and serum C peptide during the test. Thirty-three heterozygous carriers of the Ala/Val variant were identified, whereas no subjects had the variant in its homozygous form. Ala/Val carriers had a 20% reduction in serum C peptide at 30 min during the OGTT (1225+/-636 vs. 1507+/-624 pmol/L; P=0.02) compared to wild-type carriers. No significant differences in serum insulin levels during the OGTT were observed between carriers of the variant and Ala/Ala homozygotes. In conclusion, among Danish glucose-tolerant first degree relatives of type 2 diabetic patients the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1alpha gene is associated with a decreased serum C-peptide secretion during an OGTT. This finding confirms our previously reported observation of the functional importance of the variant to insulin secretion during an OGTT among middle-aged healthy subjects.

Adult↗
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↗
PubMed1998

Different genotypes causing indiscernible patterns of A expression on A(el) red blood cells as visualized by scanning immunogold electron microscopy.

BACKGROUND AND OBJECTIVES: The published sequence of the weak. A subgroup Ael gene from Swedish individuals showed a G insertion in exon VII, causing a frameshift at codon 268 (the A1 gene has 353 codons). We wished to sequence exons VI and VII of two Norwegian Ael individuals and compare the expression of A substance on RBC from different Ael individuals. MATERIALS AND METHODS: Exon VI and VII were amplified by PCR, cloned in M13 and sequenced. A structure expression on Ael RBC was studied by the immunogold technique. RESULTS: In contrast to the Swedish Ael individuals, the two Norwegians had consensus A1 sequences in exon VI and VII. However, the patterns of A expression were indiscernible from the Swedish cases as visualized by immunogold labeling in SEM. In both cases, a few (1-2%) RBC were very strongly labeled, some were weakly labeled and the majority (95%) were unlabeled. CONCLUSION: Although some Ael individuals have an inserted nucleotide in exon VII of the ABO gene, others have consensus A1 sequence in exon VI and VII. However, we could not find any differences in phenotype by immunogold labeling in SEM.

ABO Blood-Group System↗
PubMed1997

Genetic variation in the hepatocyte nuclear factor-1 alpha gene in Danish Caucasians with late-onset NIDDM.

Non-insulin-dependent diabetes mellitus (NIDDM) is a phenotypically and genetically heterogeneous disorder. A recent random genome mapping study has localized a locus termed NIDDM2 that maps to the region of chromosome 12 that includes MODY3, one of the three genes responsible for maturity-onset diabetes of the young, a monogenic form of NIDDM characterized by early age of onset and autosomal dominant inheritance. These findings suggest that NIDDM2 and MODY3 may represent different alleles of the same gene. MODY3 has recently been shown to be the gene encoding the transcription factor hepatocyte nuclear factor-1 alpha (HNF-1 alpha) thereby allowing us to determine whether mutations in the HNF-1 alpha gene are present in subjects with late-onset NIDDM. We screened 84 white NIDDM patients of Danish ancestry and found four nucleotide substitutions that changed the sequence of HNF-1 alpha, Ile27-->Leu, Ala98-->Val, Ser487-->Asn and Arg583-->Gln, five nucleotide substitutions that were silent and did not change the amino acid, Leu17, Gly288, Leu459 and Thr515, and five substitutions in the intron regions. The frequencies of the codon 27, 98 and 487 amino acid variants were similar in 245 unrelated NIDDM patients and 242 age-matched control subjects. The Arg583-->Gln mutation was found in 2 of 245 NIDDM patients and in none of the control subjects. Thus, genetic variation in the HNF-1 alpha gene is not a common factor contributing to NIDDM susceptibility in white subjects of Danish ancestry.

Age of Onset↗
PubMed1997

Chromosomal mapping and mutational analysis of the coding region of the glycogen synthase kinase-3alpha and beta isoforms in patients with NIDDM.

Activation of glycogen synthesis in skeletal muscle in response to insulin results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and activation of the protein phosphatase-1, changing the ratio between the inactive phosphorylated state of the glycogen synthase to the active dephosphorylated state. In a search for genetic defects responsible for the decreased insulin stimulated glycogen synthesis seen in patients with non-insulin-dependent diabetes mellitus (NIDDM) and their glucose-tolerant first-degree relatives we have performed mutational analysis of the coding region of the 2 isoforms of GSK-3alpha and GSK-3beta in 72 NIDDM patients and 12 control subjects. No structural changes were detected apart from a few silent mutations. Mapping of the GSK-3alpha to chromosome 19q13.1-13.2 and the GSK-3beta to chromosome 3q13.3-q21 outside known genetic loci linked to NIDDM further makes it unlikely that these genes are involved in the pathogenesis of common forms of NIDDM.

Alleles↗
PubMed1997

Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM.

Mutations in the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene cause the type 1 form of maturity onset diabetes of the young (MODY1). To address the question of whether genetic variability of HNF-4alpha is associated with late onset non-insulin-dependent diabetes mellitus (NIDDM) we have sequenced the coding region and intron/exon boundaries of the gene in 36 randomly recruited Danish NIDDM patients. Two nucleotide substitutions that changed the sequence of HNF-4alpha were identified: Thr/Ile130, which has been reported previously and a novel Val/Met255. The Val/Met 255 mutation was found in 4 of 477 Danish NIDDM patients and in none of 217 glucose tolerant control subjects; thus it cannot be excluded that this mutation may have an impact on NIDDM susceptibility. Among 509 NIDDM patients the allelic frequency of the Thr/Ile130 variant was 4.7% (95% confidence interval: 3.4-6.0%) compared to 1.9% (0.7-3.1%) among 239 control subjects (p = 0.008). However, in a population sample of 942 Swedish men with an average age of 70 years the allelic frequency of the variant was similar in 246 men with either impaired glucose tolerance (5.6% [2.6-8.6%]) or NIDDM (5.4% [2.7-8.1%]) as compared to 666 glucose tolerant men (5.1% [3.9-6.3%]). Also in a population sample of 369 young healthy Danes the prevalence of the codon 130 variant (4.7% [3.2-6.2%]) was similar to what was found in Swedish Caucasians. Thus, the allelic frequency of the Thr/Ile130 variant among the control subjects in the Danish case-control study deviates from the prevalence in the two other studies which is why we consider the significant association between the codon 130 variant and NIDDM an incidental finding. In glucose tolerant subjects the codon 130 variant in its heterozygous form had no major effect on glucose-induced insulin and C-peptide release although a tendency to a lower insulin secretion during an oral glucose tolerance test was seen in middle-aged subjects. In conclusion, variability in the coding region of the HNF-4alpha gene is not a common cause of NIDDM among whites of Danish ancestry. However, a Val/Met255 mutation was found exclusively in NIDDM patients (0.8% of cases) and functional as well as family segregation studies are needed to determine whether this HNF-4alpha variant is a NIDDM causing mutation.

Aged↗
PubMed1997

Mutational analysis of the coding region of the uncoupling protein 2 gene in obese NIDDM patients: impact of a common amino acid polymorphism on juvenile and maturity onset forms of obesity and insulin resistance.

Recently, a gene encoding a novel human uncoupling protein, designated UCP2, was discovered. The murine UCP2 was mapped to a region on mouse chromosome 7 which in several models has been shown to be linked to obesity and hyperinsulinaemia. Single strand conformation polymorphism (SSCP) analysis and direct sequencing of the coding region of the UCP2 gene in 35 obese Caucasian NIDDM patients of Danish ancestry revealed one nucleotide substitution, replacing an alanine with a valine at codon 55. The amino acid polymorphism was present in 24 of the 35 (69%) examined subjects. The allelic frequency of the A/V55 variant was 48.3% (95% CI: 42.5-54.1%) among 144 subjects with juvenile onset obesity, 45.6% (40.5-50.7%) among 182 subjects randomly selected at the draft board examination, and 45.5% (37.1-53.9%) among lean control subjects selected from the same study cohort. Within these cohorts there were no differences in BMI values at different ages among wild-type carriers and A/V55 carriers. In a population-based sample of 369 young healthy Caucasians the variant showed no association with alterations in BMI, waist-to-hip ratio, fat mass or weight gain during childhood or adolescence. The A/V55 polymorphism was not related to alterations in fasting values of serum insulin and C-peptide or to an impaired insulin sensitivity index. We conclude that genetic variability in the human UCP2 gene is not a common factor contributing to NIDDM in obese Danish Caucasian subjects and the common A/V55 amino acid polymorphism of the gene is not implicated in the pathogenesis of juvenile or maturity onset obesity or insulin resistance in Caucasians.

Adult↗
PubMed1997

Glucose tolerance status and severity of coronary artery disease in men referred to coronary arteriography.

Increasing attention is being paid to disturbances in glucose metabolism as key explanatory factors for the development of coronary artery disease. We studied the prevalence of impaired glucose tolerance and non-insulin-dependent diabetes and the levels of plasma insulin after an oral glucose tolerance test in 99 men with heart disease but without a history of diabetes referred to coronary arteriography; we also compared the outcome with a matched control group (n = 116). The severity of atherosclerosis in coronary angiograms was evaluated according to glucose tolerance status. Among the 99 patients with coronary artery disease, 37.4% had an abnormal oral glucose tolerance test result, whereas only 18.1% of the control group had an abnormal result (p < 0.01). Moreover, patients with heart disease and normal glucose tolerance were hyperinsulinemic compared with the control group (p < 0.01). By analysis of variance no statistically significant difference in severity of coronary atherosclerosis on coronary angiograms was found. In conclusion, we demonstrated frequent disturbances in glucose metabolism indicating insulin resistance in patients with ischemic heart disease without a history of diabetes, but we could not demonstrate a relation between these disturbances and degree of coronary atherosclerosis.

Adult↗
PubMed1997

Prevalence of hemochromatosis among first-time and repeat blood donors in Norway.

BACKGROUND/AIMS: The observed prevalence of hemochromatosis has ranged considerably from 0.05 to 0.37% in studies requiring liver biopsy. We aimed to study the prevalence of genetic hemochromatosis among Norwegian blood donors. METHODS: We studied 10,552 healthy blood donors (5312 women and 5240 men) using serum ferritin as a screening parameter. If serum ferritin concentration was > or = 100 micrograms/l in women and > or = 200 micrograms/l in men, serum iron and transferrin (measured as total iron binding capacity = TIBC) were measured. Blood donors who repeatedly had a transferrin saturation above 40% and a ferritin concentration above these limits were referred to a hepatologist (H.B.). RESULTS: Serum ferritin was > or = 100 micrograms/l in 94/5312 (1.8%) women and > or = 200 microliters in 79/5240 (1.5%) men. Of these, 37 persons had a serum ferritin concentration above 100 micrograms/l (females) or above 200 micrograms/l (males) and a transferrin saturation above 40%. Nineteen of them (13 men and 6 women, median age 36 years, range 28-68) were identified as having hemochromatosis on the basis of increased hepatic iron index. Serum ferritin ranged from 111 to 1980 micrograms/l (median 357 micrograms/l and transferrin saturation from 50 to 100% (median 92%), hepatic iron from 48 to 471 mumol/g dry weight (median 118 mumol/g) and hepatic iron index from 1.5 to 12.1 (median 3.0). One person had cirrhosis and none had diabetes. The prevalence of hemochromatosis was significantly higher among first-time blood donors (12 out of 3500 [3.4/1000]) compared with repeat donors (7 out of 7052 [1/1000]), p < 0.005. CONCLUSIONS: The observed prevalence of hemochromatosis in Norwegian first-time blood donors of 0.34% is comparable to recently observed prevalences in other studies. However, the use of serum ferritin as a first-step screening tool may have failed to detect hemochromatosis in the early stage where iron overload has not yet occurred.

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↗