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The -238 and -308 G-->A polymorphisms of the tumor necrosis factor alpha gene promoter are not associated with features of the insulin resistance syndrome or altered birth weight in Danish Caucasians.

https://arctichealth.org/en/permalink/ahliterature47878
Source
J Clin Endocrinol Metab. 2000 Apr;85(4):1731-4
Publication Type
Article
Date
Apr-2000
Author
S K Rasmussen
S A Urhammer
J N Jensen
T. Hansen
K. Borch-Johnsen
O. Pedersen
Author Affiliation
Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark.
Source
J Clin Endocrinol Metab. 2000 Apr;85(4):1731-4
Date
Apr-2000
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Birth Weight - genetics
Body constitution
Body mass index
Denmark
Diabetes Mellitus, Type 2 - genetics
Female
Genotype
Humans
Insulin - blood
Insulin Resistance - genetics
Lipids - blood
Male
Obesity - genetics
Polymorphism, Restriction Fragment Length
Promoter Regions (Genetics)
Research Support, Non-U.S. Gov't
Tumor Necrosis Factor-alpha - genetics
Abstract
Recently, two G-->A polymorphisms at positions -308 and -238, in the promoter of the tumor necrosis factor alpha (TNF-alpha) gene, have been identified. These variants have, in different ethnic groups, been linked to estimates of insulin resistance and obesity. The objective of the present study was to investigate whether these genetic variants of TNF-alpha were associated with features of the insulin resistance syndrome or alterations in birth weight in two Danish study populations comprising 380 unrelated young healthy subjects and 249 glucose-tolerant relatives of type 2 diabetic patients, respectively. All study participants underwent an iv glucose tolerance test with the addition of tolbutamide after 20 min. In addition, a number of biochemical and anthropometric measures were performed on each subject. The subjects were genotyped for the polymorphisms by applying PCR restriction fragment length polymorphism. Neither of the variants was related to altered insulin sensitivity index or other features of the insulin resistance syndrome (body mass index, waist to hip ratio, fat mass, fasting serum lipids or fasting serum insulin or C-peptide). Birth weight and the ponderal index were also not associated with the polymorphisms. In conclusion, although the study was carried out on sufficiently large study samples, the study does not support a major role of the -308 or -238 substitutions of the TNF-alpha gene in the pathogenesis of insulin resistance or altered birth weight among Danish Caucasian subjects.
PubMed ID
10770222 View in PubMed
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Genetic variation in the hepatocyte nuclear factor-1 alpha gene in Danish Caucasians with late-onset NIDDM.

https://arctichealth.org/en/permalink/ahliterature48182
Source
Diabetologia. 1997 Apr;40(4):473-5
Publication Type
Article
Date
Apr-1997
Author
S A Urhammer
S K Rasmussen
P J Kaisaki
N. Oda
K. Yamagata
A M Møller
M. Fridberg
L. Hansen
T. Hansen
G I Bell
O. Pedersen
Author Affiliation
Steno Diabetes Center, Copenhagen, Denmark.
Source
Diabetologia. 1997 Apr;40(4):473-5
Date
Apr-1997
Language
English
Publication Type
Article
Keywords
Age of Onset
Base Sequence
Chromosome Mapping
Chromosomes, Human, Pair 12
Codon
DNA Primers
DNA-Binding Proteins - genetics
Denmark
Diabetes Mellitus, Type 2 - genetics
European Continental Ancestry Group - genetics
Exons
Female
Gene Frequency
Hepatocyte Nuclear Factor 1
Hepatocyte Nuclear Factor 1-alpha
Hepatocyte Nuclear Factor 1-beta
Humans
Male
Middle Aged
Nuclear Proteins
Point Mutation
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Research Support, Non-U.S. Gov't
Transcription Factors - genetics
Variation (Genetics)
Abstract
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.
PubMed ID
9112026 View in PubMed
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The K121Q variant of the human PC-1 gene is not associated with insulin resistance or type 2 diabetes among Danish Caucasians.

https://arctichealth.org/en/permalink/ahliterature47821
Source
Diabetes. 2000 Sep;49(9):1608-11
Publication Type
Article
Date
Sep-2000
Author
S K Rasmussen
S A Urhammer
A. Pizzuti
S M Echwald
C T Ekstrøm
L. Hansen
T. Hansen
K. Borch-Johnsen
L. Frittitta
V. Trischitta
O. Pedersen
Author Affiliation
Steno Diabetes Center and Hagedorn Research Institute, Copenhagen, Denmark.
Source
Diabetes. 2000 Sep;49(9):1608-11
Date
Sep-2000
Language
English
Publication Type
Article
Keywords
Adult
Aged
Amino Acid Substitution
Blood Glucose - metabolism
Denmark
Diabetes Mellitus, Type 2 - genetics
European Continental Ancestry Group - genetics
Female
Heterozygote
Homozygote
Humans
Insulin - blood
Insulin Resistance - genetics
Male
Membrane Glycoproteins - genetics
Middle Aged
Phosphoric Diester Hydrolases
Pyrophosphatases
Research Support, Non-U.S. Gov't
Variation (Genetics)
Abstract
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.
PubMed ID
10969849 View in PubMed
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Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release.

https://arctichealth.org/en/permalink/ahliterature47231
Source
Diabetologia. 2004 Jun;47(6):1079-87
Publication Type
Article
Date
Jun-2004
Author
S K Hansen
A P Gjesing
S K Rasmussen
C. Glümer
S A Urhammer
G. Andersen
C S Rose
T. Drivsholm
S K Torekov
D P Jensen
C T Ekstrøm
K. Borch-Johnsen
T. Jørgensen
M I McCarthy
T. Hansen
O. Pedersen
Author Affiliation
Steno Diabetes Center and Hagedorn Research Institute, Niels Steensens Vej 2, 2820 Gentofte, Denmark. sakf@steno.dk
Source
Diabetologia. 2004 Jun;47(6):1079-87
Date
Jun-2004
Language
English
Publication Type
Article
Keywords
Adult
Alleles
Birth Weight - physiology
Blood Glucose - chemistry - metabolism
Case-Control Studies
Comparative Study
Denmark - ethnology
Diabetes Mellitus, Type 2 - genetics - physiopathology
European Continental Ancestry Group - genetics
Female
Genotype
Glycosyltransferases - genetics - metabolism
Humans
Insulin - genetics - metabolism
Male
Middle Aged
Minisatellite Repeats - genetics
Polymorphism, Genetic
Research Support, Non-U.S. Gov't
Abstract
AIMS/HYPOTHESIS: The class III allele of the variable-number-of-tandem-repeats polymorphism located 5' of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose-induced insulin response among NGT individuals. METHODS: We investigated the impact of the class III allele on Type 2 diabetes susceptibility in a case-control study involving 1462 Type 2 diabetic patients and 4931 NGT subjects. We also examined the potential impact of the class III allele in genotype-quantitative trait studies in three Danish study populations containing (i) 358 young healthy subjects; (ii) 4444 middle-aged NGT subjects, 490 subjects with IFG and 678 subjects with IGT; and (iii) 221 NGT subjects, of whom one parent had Type 2 diabetes. RESULTS: There was no difference in frequency of the class III allele or in genotype distribution between the 1462 Type 2 diabetic patients and the 4931 NGT subjects. Among the 358 young subjects the class III/III carriers had significantly reduced post-IVGTT acute serum insulin and C-peptide responses (p=0.04 and 0.03 respectively). However, among the 4444 middle-aged subjects we failed to demonstrate any association between the class III allele and post-OGTT serum insulin and C-peptide levels. CONCLUSIONS/INTERPRETATION: The class III allele of the INS-VNTR does not confer susceptibility to Type 2 diabetes or consistent alterations in glucose-induced insulin release in the examined populations, which consisted of Danish Caucasians.
PubMed ID
15170498 View in PubMed
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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.

https://arctichealth.org/en/permalink/ahliterature47879
Source
J Clin Endocrinol Metab. 2000 Apr;85(4):1606-10
Publication Type
Article
Date
Apr-2000
Author
S K Rasmussen
C. Lautier
L. Hansen
S M Echwald
T. Hansen
C T Ekstrøm
S A Urhammer
K. Borch-Johnsen
F. Grigorescu
R J Smith
O. Pedersen
Author Affiliation
Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark.
Source
J Clin Endocrinol Metab. 2000 Apr;85(4):1606-10
Date
Apr-2000
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Alleles
Birth weight
Codon
DNA Mutational Analysis
Denmark
Diabetes Mellitus, Type 2 - genetics
Female
Gene Frequency
Humans
Insulin - blood - pharmacology
Insulin-Like Growth Factor I - genetics
Male
Middle Aged
Mutation
Polymorphism, Genetic
Receptor, IGF Type 1 - genetics
Research Support, Non-U.S. Gov't
Abstract
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.
PubMed ID
10770205 View in PubMed
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Variability of the insulin receptor substrate-1, hepatocyte nuclear factor-1alpha (HNF-1alpha), HNF-4alpha, and HNF-6 genes and size at birth in a population-based sample of young Danish subjects.

https://arctichealth.org/en/permalink/ahliterature47828
Source
J Clin Endocrinol Metab. 2000 Aug;85(8):2951-3
Publication Type
Article
Date
Aug-2000
Author
S K Rasmussen
S A Urhammer
T. Hansen
K. Almind
A M Møller
K. Borch-Johnsen
O. Pedersen
Author Affiliation
Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark.
Source
J Clin Endocrinol Metab. 2000 Aug;85(8):2951-3
Date
Aug-2000
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Amino Acid Substitution
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Birth Weight - genetics
Body Constitution - genetics
Body Height - genetics
DNA-Binding Proteins - genetics
Denmark
European Continental Ancestry Group - genetics
Hepatocyte Nuclear Factor 1
Hepatocyte Nuclear Factor 1-alpha
Hepatocyte Nuclear Factor 1-beta
Hepatocyte Nuclear Factor 4
Hepatocyte Nuclear Factor 6
Homeodomain Proteins - genetics
Humans
Nuclear Proteins
Phosphoproteins - genetics
Polymorphism, Genetic
Research Support, Non-U.S. Gov't
Trans-Activators - genetics
Transcription Factors - genetics
Variation (Genetics)
Abstract
Reduced size at birth has been proposed to be a risk factor for insulin resistance and type 2 diabetes. It is, however, not known whether this association is explained by unfavorable intrauterine environment or by specific susceptibility genotypes predisposing for both reduced fetal growth and insulin resistance and type 2 diabetes. The present study was performed to evaluate whether previously identified amino acid polymorphisms of genes that from animal models have been suggested to play important roles during fetal development are associated with alterations in size at birth. The study population comprised 380 subjects randomly recruited from a population of young Danish Caucasian individuals, aged 18-32 yr. The original data of birth length and weight for 331 of 380 subjects were obtained from the midwife records. The Gly/Arg972 of insulin receptor substrate-1 (IRS-1), the Thr/Ile130 of the hepatocyte nuclear factor-4alpha (HNF-4alpha), the Pro/Ala75 of HNF-6, and the Ile/Leu27, Ala/Val93, and Ser/Asn4s7 polymorphisms of the HNF-lalpha gene were examined for association with birth weight and length and the ponderal index. Using a generalized linear model, including gender and the genotype as fixed variables, and applying Bonferroni correction for multiple testing, we could not demonstrate any significant differences in these estimates among wild-type, heterozygous, and homozygous carriers with respect to any of the gene variants. In conclusion, common variability in the genes encoding the IRS-1, HNF-lalpha, HNF-4alpha, and HNF-6 proteins can be excluded as major factors influencing size at birth among Danish Caucasian subjects.
PubMed ID
10946909 View in PubMed
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7 records – page 1 of 1.