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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
Less detail

Amino acid polymorphisms in the ATP-regulatable inward rectifier Kir6.2 and their relationships to glucose- and tolbutamide-induced insulin secretion, the insulin sensitivity index, and NIDDM.

https://arctichealth.org/en/permalink/ahliterature48195
Source
Diabetes. 1997 Mar;46(3):508-12
Publication Type
Article
Date
Mar-1997
Author
L. Hansen
S M Echwald
T. Hansen
S A Urhammer
J O Clausen
O. Pedersen
Author Affiliation
Steno Diabetes Center and the Hagedorn Research Institute, Glostrup University Hospital, Copenhagen, Denmark.
Source
Diabetes. 1997 Mar;46(3):508-12
Date
Mar-1997
Language
English
Publication Type
Article
Keywords
Adenosine Triphosphate - metabolism
Adult
Blood Glucose - metabolism
C-Peptide - blood
Cohort Studies
DNA Primers
Denmark
Diabetes Mellitus, Type 2 - blood - genetics - physiopathology
European Continental Ancestry Group
Female
Glucose Tolerance Test
Humans
Hypoglycemic Agents - pharmacology
Insulin - blood - secretion
Male
Polymerase Chain Reaction
Polymorphism, Genetic
Polymorphism, Single-Stranded Conformational
Potassium Channels - genetics - metabolism
Potassium Channels, Inwardly Rectifying
Reference Values
Research Support, Non-U.S. Gov't
Tolbutamide - pharmacology
Abstract
Kir6.2 is an inwardly rectifying potassium channel that is expressed in pancreatic beta-cells and cardiac and skeletal muscle. Expressed together with the high-affinity sulphonylurea receptor, it reconstitutes a sulphonylurea- and also ATP-sensitive potassium channel resembling the native beta-cell channel. The objective of this study was to search for mutations in the Kir6.2 gene that might be associated with NIDDM or related to altered insulin secretion, insulin action, or glucose metabolism in healthy subjects. Using polymerase chain reaction-single-strand conformation polymorphism analysis (PCR-SSCP) on genomic DNA from 69 Danish NIDDM patients and 66 matched control subjects, we report the finding of three missense polymorphisms in otherwise conserved codons and three silent polymorphisms in the gene encoding Kir6.2: codon 23 (GAG/AAG), Glu-->Lys; codon 190 (GCT/GCC), Ala-->Ala; codon 267 (CTC/CTG), Leu-->Leu; codon 270 (CTG/GTG), Leu-->Val; codon 337 (ATC/GTC), Ile-->Val; codon 381 (AAG/AAA), Lys-->Lys. The codon 23 and codon 337 amino acid polymorphisms were always coupled. The allelic frequencies of the polymorphisms were similar in NIDDM patients and control subjects. The amino acid polymorphisms were not associated with altered insulin secretion after intravenous glucose or tolbutamide injections or with altered glucose effectiveness in a phenotype study of 346 young healthy subjects. However, carriers of the maximal load of amino acid variants, the compound homozygous codon 23/337 and heterozygous codon 270, had on average a 62% higher insulin sensitivity index (P = 0.006), compared with noncarriers. We conclude that a combination of common Kir6.2 amino acid variants may contribute to the genetic background behind the large variation of the insulin sensitivity index in the general population.
PubMed ID
9032110 View in PubMed
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The common T60N polymorphism of the lymphotoxin-alpha gene is associated with type 2 diabetes and other phenotypes of the metabolic syndrome.

https://arctichealth.org/en/permalink/ahliterature47106
Source
Diabetologia. 2005 Mar;48(3):445-51
Publication Type
Article
Date
Mar-2005
Author
Y H Hamid
S A Urhammer
C. Glümer
K. Borch-Johnsen
T. Jørgensen
T. Hansen
O. Pedersen
Author Affiliation
Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark. yah@steno.dk
Source
Diabetologia. 2005 Mar;48(3):445-51
Date
Mar-2005
Language
English
Publication Type
Article
Keywords
Adult
Age of Onset
Blood Glucose - metabolism
Cohort Studies
Denmark - epidemiology
Diabetes Mellitus, Type 1 - drug therapy - genetics
European Continental Ancestry Group
Female
Humans
Insulin - therapeutic use
Lymphotoxin - genetics
Male
Metabolic Syndrome X - genetics
Middle Aged
Phenotype
Polymorphism, Single Nucleotide
Reference Values
Research Support, Non-U.S. Gov't
Abstract
AIMS/HYPOTHESIS: Associations between variations in the lymphotoxin-alpha gene (LTA) and myocardial infarction, cerebral infarction and type 1 diabetes have previously been reported. We hypothesised that, in its homozygous form, the functional T60N variant of LTA is associated with type 2 diabetes and other features of the metabolic syndrome among Danish Caucasian individuals. METHODS: The T60N polymorphism of LTA was genotyped in the population-based Inter99 study cohort (6,514 Caucasian subjects) and in a group of type 2 diabetic patients by analysis of PCR-generated primer extension products using high-throughput chip-based matrix-assisted laser desorption/ionisation time-of-flight mass spectronomy. RESULTS: Comparison of 1,401 diabetic patients with 1,470 matched glucose-tolerant control subjects from the Inter99 cohort revealed that the frequency of the mutant at codon 60 in its homozygous form (N/N genotype) was higher among the diabetic patients than among the control subjects (14.6% [95% CI 12.8-16.5] vs 12.0% [95% CI 10.3-13.7], p=0.048; odds ratio=1.24). This association was even stronger among the 131 patients with early-onset (diagnosis at 40 years or younger) diabetes (21.4% [95% CI 14.4-28.4] vs 12.0% [95% CI 10.3-13.7], p=0.004; odds ratio=1.99). Additionally, studies of the metabolic syndrome (as defined by the 1999 World Health Organization criteria) in the Inter99 study cohort revealed that the frequency of the N/N LTA genotype was higher among subjects presenting one or more features of the metabolic syndrome (n=4,425) than among subjects with no characteristics of this syndrome (n=1,752) (p=0.026). CONCLUSIONS/INTERPRETATION: The T60N LTA polymorphism is associated with type 2 diabetes and other features of the metabolic syndrome among Caucasian individuals.
PubMed ID
15729581 View in PubMed
Less detail

Fasting and oral glucose-stimulated levels of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are highly familial traits.

https://arctichealth.org/en/permalink/ahliterature126848
Source
Diabetologia. 2012 May;55(5):1338-45
Publication Type
Article
Date
May-2012
Author
A P Gjesing
C T Ekstrøm
H. Eiberg
S A Urhammer
J J Holst
O. Pedersen
T. Hansen
Author Affiliation
Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Universitetsparken 1, DK-2100 Copenhagen, Denmark. anette.gjesing@sund.ku.dk
Source
Diabetologia. 2012 May;55(5):1338-45
Date
May-2012
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Blood Glucose - metabolism
C-Peptide - blood
Denmark - epidemiology
Diabetes Mellitus, Type 2 - blood - genetics - metabolism
Fasting
Female
Gastric Inhibitory Polypeptide - blood
Glucagon-Like Peptide 1 - blood
Glucose Tolerance Test
Humans
Insulin - blood - secretion
Insulin-Secreting Cells - metabolism
Male
Middle Aged
Abstract
Heritability estimates have shown a varying degree of genetic contribution to traits related to type 2 diabetes. Therefore, the objective of this study was to investigate the familiality of fasting and stimulated measures of plasma glucose, serum insulin, serum C-peptide, plasma glucose-dependent insulinotropic polypeptide (GIP) and plasma glucagon-like peptide-1 (GLP-1) among non-diabetic relatives of Danish type 2 diabetic patients.
Sixty-one families comprising 193 non-diabetic offspring, 29 non-diabetic spouses, 72 non-diabetic relatives (parent, sibling, etc.) and two non-related relatives underwent a 4 h 75 g OGTT with measurements of plasma glucose, serum insulin, serum C-peptide, plasma GIP and plasma GLP-1 levels at 18 time points. Insulin secretion rates (ISR) and beta cell responses to glucose, GIP and GLP-1 were calculated. Familiality was estimated based on OGTT-derived measures.
A high level of familiality was observed during the OGTT for plasma levels of GIP and GLP-1, with peak familiality values of 74 ? 16% and 65 ? 15%, respectively (h (2) ? SE). Familiality values were lower for plasma glucose, serum insulin and serum C-peptide during the OGTT (range 8-48%, 14-44% and 15-61%, respectively). ISR presented the highest familiality value at fasting reaching 59 ? 16%. Beta cell responsiveness to glucose, GLP-1 and GIP also revealed a strong genetic influence, with peak familiality estimates of 62 ? 13%, 76 ? 15% and 70 ? 14%, respectively.
Our results suggest that circulating levels of GIP and GLP-1 as well as beta cell response to these incretins are highly familial compared with more commonly investigated measures of glucose homeostasis such as fasting and stimulated plasma glucose, serum insulin and serum C-peptide.
PubMed ID
22349073 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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Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor-gamma2 (PPAR-gamma2): divergent modulating effects on body mass index in obese and lean Caucasian men.

https://arctichealth.org/en/permalink/ahliterature201202
Source
Diabetologia. 1999 Jul;42(7):892-5
Publication Type
Article
Date
Jul-1999
Author
J. Ek
S A Urhammer
T I Sørensen
T. Andersen
J. Auwerx
O. Pedersen
Author Affiliation
Steno Diabetes Center and Hagedorn Research Institute, Copenhagen, Denmark.
Source
Diabetologia. 1999 Jul;42(7):892-5
Date
Jul-1999
Language
English
Publication Type
Article
Keywords
Adult
Body mass index
Cohort Studies
Denmark - epidemiology
European Continental Ancestry Group - genetics
Genetic Variation
Homozygote
Humans
Male
Microbodies - genetics
Middle Aged
Mutation - genetics
Obesity - etiology
Polymorphism, Genetic
Receptors, Cytoplasmic and Nuclear - genetics
Transcription Factors - genetics
Abstract
The objectives of the present investigation were to examine: 1) whether a Pro115Gln variant in the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with juvenile-onset obesity among Danish Caucasianmen and 2) whether the relation of a Pro12Ala polymorphism in PPAR-gamma2 with BMI and long-term weight regulation differ between lean and obese subjects within the same cohort.
The Pro115Gln and Pro112Ala variants were examined using PCR and RFLP in a group of 752 subjects with a Body Mass Index (BMI) of 31.0 kg/m2 or more and in 869 non-obese control subjects.
We did not find Pro115Gln in any of the 1621 male subjects we examined. Among the males with juvenile-onset obesity, the allelic frequency of the Pro12Ala polymorphism was 14% (95% confidence interval: 12-16%) compared with 16% (14-17%) among the non-obese control subjects (NS). Heterozygosity of the codon 12 variant was not associated with differences in BMI or changes in body weight regulation during follow up in lean or obese subjects. In the group of obese subjects, 21 homozygous Ala12Ala carriers had, however, a higher BMI (38.9 +/- 5.4 kg/m2 (means +/- SD) vs 35.5 +/- 5.5 kg/ m2, p = 0.008) and a higher weight gain (0.27 +/- 0.24 kg x m(-2) x year(-1) vs 0.10 +/- 0.24 kg x m(-2) x year(-1), p = 0.004), compared with wild-type carriers. Moreover, within the control group of 869 men the 14 homozygous carriers of the variant had a lower BMI (24.4 +/- 2.7 kg/m2 vs 26.2 +/- 3.7 kg/m2, p = 0.005) and a slower increase in BMI (0.11 +/- 0.11 kg x m(-2) x year(-1) vs 0.17 +/- 0.11 kg x m(-2) x year(-1), p = 0.002) compared with wild-type carriers.
The codon 12 variant of PPAR-gamma2 is not intrinsically associated with juvenile obesity. The variant may in its homozygous form interact, however, with various combinations of genetic and environmental factors in lean and obese subjects to cause divergent modulating effects on BMI and long-term body weight control.
PubMed ID
10440134 View in PubMed
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Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index.

https://arctichealth.org/en/permalink/ahliterature11089
Source
Diabetes. 1997 Mar;46(3):494-501
Publication Type
Article
Date
Mar-1997
Author
T. Hansen
C B Andersen
S M Echwald
S A Urhammer
J O Clausen
H. Vestergaard
D. Owens
L. Hansen
O. Pedersen
Author Affiliation
Steno Diabetes Center and Hagedorn Research Institute, Glostrup University Hospital, Copenhagen, Denmark.
Source
Diabetes. 1997 Mar;46(3):494-501
Date
Mar-1997
Language
English
Publication Type
Article
Keywords
1-Phosphatidylinositol 3-Kinase
Adolescent
Adult
Blood Glucose - metabolism
Blood pressure
C-Peptide - blood
Child
DNA - blood
DNA Primers
Denmark
Diabetes Mellitus, Type 2 - blood - enzymology - genetics
European Continental Ancestry Group
Genotype
Heterozygote
Homozygote
Humans
Insulin - blood
Isoleucine
Macromolecular Substances
Methionine
Muscle, Skeletal - enzymology
Phosphotransferases (Alcohol Group Acceptor) - chemistry - genetics
Polymerase Chain Reaction
Polymorphism, Genetic
Polymorphism, Single-Stranded Conformational
Reference Values
Research Support, Non-U.S. Gov't
Variation (Genetics)
Abstract
Phosphatidylinositol 3-kinase (PI3-K) may regulate the basal plasma membrane glucose transporter recycling and the organization of the transporter intracellular pool in addition to being an insulin signal for translocation of glucose transporters to the plasma membrane. The objectives of the present study were to examine for genetic variability in the human regulatory p85alpha subunit of PI3-K, to look for an association between gene variants and NIDDM in a case-control study, and to relate identified variability to potential changes in whole-body insulin sensitivity and glucose turnover in a phenotype study. Single-strand conformational polymorphism and heteroduplex analysis of the coding region of the regulatory p85alpha subunit in cDNA isolated from human muscle tissue from 70 insulin-resistant NIDDM patients and 12 control subjects revealed three silent polymorphisms and a missense mutation at nucleotide position 1020 (G-->A), changing a Met to Ile at codon 326. Using allele-specific oligohybridization, we found a similar allelic frequency of the codon 326Met-->Ile variant in 404 NIDDM patients (0.15 [95% CI 0.13-0.17]) and 224 matched glucose tolerant control subjects (0.16 [0.13-0.19]). In a random sample of 380 unrelated healthy young Caucasians aged 18-32 years, in whom we have performed a tolbutamide modified intravenous glucose tolerance test, we identified 263 wildtype subjects, 109 heterozygous subjects, and 8 subjects homozygous for the codon 326 variant (allelic frequency = 0.16 [0.13-0.19]). No difference in glucose disappearance constant (KG), insulin sensitivity index (SI), and glucose effectiveness (SG) was observed between wildtype and heterozygous subjects. However, compared with the combined values for wildtype and heterozygous carriers, KG was reduced by 40% (P = 0.004) and SG by 23% (P = 0.03) in homozygous carriers of the p85alpha variant. Moreover, in homozygous carriers, a 32% reduction was found in SI (P = 0.08). In conclusion, a codon 326Met-->Ile variant in the gene encoding the PI3-K p85alpha regulatory subunit is found in 31% of a random sample of young healthy Caucasians. About 2% of the subjects in this population carry the gene variant in its homozygous form, and these carriers are characterized by significant reductions in whole-body glucose effectiveness and intravenous glucose disappearance constant. In itself, the gene variant does not confer an increased risk of diabetes.
PubMed ID
9032108 View in PubMed
Less detail

Insulin sensitivity and body weight changes in young white carriers of the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor gene.

https://arctichealth.org/en/permalink/ahliterature211439
Source
Diabetes. 1996 Aug;45(8):1115-20
Publication Type
Article
Date
Aug-1996
Author
S A Urhammer
J O Clausen
T. Hansen
O. Pedersen
Author Affiliation
Steno Diabetes Center, Medical Department C, Glostrup Hospital, University of Copenhagen, Denmark.
Source
Diabetes. 1996 Aug;45(8):1115-20
Date
Aug-1996
Language
English
Publication Type
Article
Keywords
Adult
Birth weight
Body Weight
C-Peptide - blood
Denmark
Female
Gene Frequency
Glucose - metabolism
Heterozygote
Homozygote
Humans
Insulin - blood
Insulin Resistance
Male
Obesity - genetics
Point Mutation
Polymorphism, Genetic
Receptors, Adrenergic, beta - genetics
Abstract
Recently, a missense mutation replacing tryptophan with arginine at codon 64 of the beta 3-adrenergic receptor gene was shown to be associated with insulin resistance in nondiabetic subjects and to an earlier onset of NIDDM in Pima Indians. We studied whether the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor gene in a cohort of young healthy Danes was associated with high birth weight, accelerated weight gain during childhood and adolescence, present obesity, or impaired insulin sensitivity. The protocol included 380 unrelated white subjects in whom insulin sensitivity and secretion were measured during a combined intravenous glucose and tolbutamide tolerance test. A number of biochemical and anthropometric characteristics were determined for each subject. The subjects were genotyped for the codon 64 polymorphism by applying polymerase chain reaction restriction fragment-length polymorphism screening with the use of endonuclease BstN1. The allelic frequency of the mutated allele was 7% (95% CI: 5-10%), and it was similar in obese and nonobese subjects. The beta 3-adrenergic receptor gene variant was not related to birth weight or weight gain during childhood or adolescence. In its heterozygous form, the gene variant was not associated with an altered insulin sensitivity index (SI) or other features of the insulin resistance syndrome (BMI, blood pressure, fasting serum lipid levels, or fasting serum fibrinolytic variables). Three homozygous carriers of the polymorphism were identified, and each had a significantly higher BMI (27.4 +/- 1.3 vs. 23.5 +/- 3.7 kg/m2 [mean +/- SD]; P = 0.032), lower SI [4.9 +/- 2.9 vs. 15.4 +/- 9.0 10(-5) x (min x pmol/l)-1; P = 0.013], and higher fasting serum C-peptide (730 +/- 155 vs. 471 +/- 158 pmol/l; P = 0.016) than the wild-type carriers. The homozygous carriers also had significantly higher levels of fasting serum triglyceride (P = 0.042) and serum LDL cholesterol (P = 0.013). When adjustments were made for age, sex, BMI, and VO2max in a multiple regression analysis, a significantly negative association was found between homozygosity for the codon 64 variant and the SI (P = 0.009). We conclude that in young healthy Danes, the homozygous form but not the heterozygous form of the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor may be associated with obesity and, independent of BMI, with a low SI. Since only three homozygous carriers were identified among 380 subjects, the results must be interpreted with caution, and studies of larger population samples are needed.
PubMed ID
8690160 View in PubMed
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Intermediate expansions of a GAA repeat in the frataxin gene are not associated with type 2 diabetes or altered glucose-induced beta-cell function in Danish Caucasians.

https://arctichealth.org/en/permalink/ahliterature10704
Source
Diabetes. 1999 Apr;48(4):914-7
Publication Type
Article
Date
Apr-1999
Author
L T Dalgaard
T. Hansen
S A Urhammer
J O Clausen
H. Eiberg
O. Pedersen
Author Affiliation
Steno Diabetes Center, Glostrup University Hospital, Denmark.
Source
Diabetes. 1999 Apr;48(4):914-7
Date
Apr-1999
Language
English
Publication Type
Article
Keywords
Adult
Denmark
Diabetes Mellitus, Type 2 - genetics
European Continental Ancestry Group - genetics
Female
Glucose - pharmacology
Humans
Iron-Binding Proteins
Islets of Langerhans - drug effects
Male
Middle Aged
Phosphotransferases (Alcohol Group Acceptor) - genetics
Research Support, Non-U.S. Gov't
Trinucleotide Repeat Expansion - physiology
Abstract
A variable expansion of a GAA repeat is present in the first intron of the frataxin gene, also termed FRDA1 or X25. Long repeat lengths (>66 repeats) are present in patients with Friedreich's ataxia, while an intermediate expansion (10-66 repeats) has recently been reported to be highly associated with type 2 diabetes. Using a polymerase chain reaction-based assay, we found that 32.4% (95%CI 29.9-34.9) of 636 Danish Caucasian type 2 diabetic patients were carriers of an intermediate expansion, whereas the frequency was 30.4% (26.4-34.4) among 224 matched glucose-tolerant control subjects (P = 0.6). In the control subjects, the values of serum insulin and C-peptide responses during an oral glucose tolerance test were similar between the 69 carriers and 155 noncarriers. Furthermore, we investigated a possible relationship between expansions of the FRDA1 gene and glucose-induced beta-cell function in 338 young Caucasians (33.7% [30.1-37.3] carriers) and in 215 glucose-tolerant subjects (31.0% [26.6-35.4] carriers) with a type 2 diabetic parent. In neither population did the carriers differ from noncarriers according to values of fasting plasma glucose, serum insulin, or C-peptide, acute serum insulin, or C-peptide responses after intravenous glucose. In conclusion, intermediate expansion of the frataxin trinucleotide repeat is not associated with type 2 diabetes or altered glucose-induced insulin secretion in Danish Caucasians.
PubMed ID
10102712 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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22 records – page 1 of 3.