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  • 1
    Electronic Resource
    Electronic Resource
    The Effect of HLA and Insulin-Dependent Diabetes Mellitus on the Secretion Levels of Tumour Necrosis Factors Alpha and Beta and Gamma Interferon (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 32 (1990), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Tumour necrosis factors alpha and beta (TNF-α and TNF-β) and gamma interferon (IFN-γ) were measured by ELISA in the supernatants of phytohaemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMNC) from 98 individuals (60 controls and 38 patients with insulin-dependent diabetes mellitus [IDDM]. The PBMNC were incubated with varying concentrations of PHA (0,1,5, and 10 μg/ml) for 72 h. In our population study we observed a correlation between the levels of secretion of TNF-α and IFN-γ but not TNF-β. The complete data set was analysed by non-parametric tests, and no associations with HLA phenotypes existed. Reduced levels of TNF-β, but not TNF-α or IFN-γ, secretion were found in IDDM patients stimulated with 1 and 5 μg/ml of PHA (P -0.001 and 0.02 respectively). None of the lymphokine secretion levels at any PHA concentration correlated with particular HLA phenotypes.Analysis of the natural log-transformed data indicated that only for the TNF-β levels (at 5 μg/ml PHA) could subjects be divided into high and low secretors, which also did not correlate with a particular HLA-B or -DR antigen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1990.tb03213.x
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  • 2
    Electronic Resource
    Electronic Resource
    THE EFFECT OF TNF*B GENE POLYMORPHISM ON TNF-α AND -β SECRETION LEVELS IN PATIENTS WITH INSULIN-DEPENDENT DIABETES MELLITUS AND HEALTHY CONTROLS (1996)
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 23 (1996), S. 0 
    Details
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: TNF-α and -β have been implicated in the development of HLA-associated autoimmune diseases. It has been suggested that inter-individual differences in the secretion levels of these cytokines may contribute to the predisposition of certain individuals to the development of diseases such as insulin-dependent diabetes mellitus (IDDM). We have investigated whether a diallelic TNF*B polymorphism detected using the enzyme Ncol influences the TNF-α and/or -β secretory capacity of peripheral blood mononuclear cells (PBMC) from PHA stimulated healthy individuals and IDDM patients.We have shown that the level of TNF-β secreted correlates with the TNF*B genotype in healthy individuals: those with the TNF B*2 allele secreted significantly higher levels of TNF-β (P= 0.025) than those with the TNF*B1 allele. In IDDM patients, the reverse situation was observed, with those patients with the TNF*B1 allele secreting higher levels of TNF-β than those with the TNF*B2 allele. No correlation was found between TNF-α levels and TNF*B genotype. Furthermore, when IDDM patients and controls were matched for TNF*B genotype, the IDDM patients with the TNF*B2 allele secreted significantly lower levels of TNF-β than controls with this allele.On analysis of IDDM-susceptible extended HLA haplotypes in the homozygous groups, 4/7 IDDM patients with the TNF*B2 allele were Bw62-DR4 compared with 0/16 matched controls. Thus, the extended haplotype Bw62-DR4-TNF*B2/2 rather than IDDM per se is almost certainly responsible for the depressed TNF-β secretion found in the IDDM-TNF*B2 homozygous cohort.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1744-313X.1996.tb00133.x
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  • 3
    Electronic Resource
    Electronic Resource
    Genetic contribution of polymorphism of the GLUT1 and GLUT4 genes to the susceptibility to type 2 (non-insulin-dependent) diabetes mellitus in different populations (1996)
    Springer
    Acta diabetologica 33 (1996), S. 193-197 
    Details
    ISSN: 1432-5233
    Keywords: Key words Glucose transporter glycoproteins ; Non-insulin-dependent diabetes ; Genetic polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Polymorphic variation of genes encoding the glucose transporters glycoproteins (GLUT) may contribute to the genetic susceptibility to type 2 (non-insulin-dependent) diabetes. In this study we evaluated the allele and genotype frequencies of GLUT1 and GLUT4 restriction fragment length polymorphism (RFLP), revealed by digestion with XbaI for GLUT1 and KpnI for GLUT4, in Caucasian, Chinese, Japanese, Asian Indian and American black populations. No differences of the KpnI GLUT 4 RFLP were found between control and diabetic subjects in any ethnic group or when all data are combined. In contrast, positive results were found for the XbaI RFLP: (1) most ethnic groups showed an association of allele 1 with type 2 diabetes, and this association was maintained when all groups were analysed together; (2) after stratifying for sex and obesity, this association was significant only for overweight/obese women. This joint analysis suggests that GLUT1 polymorphism may contribute to susceptibility to type 2 diabetes in some populations, and especially in overweight/obese women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02048542
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  • 4
    Electronic Resource
    Electronic Resource
    Genetic contribution of polymorphism of the GLUT1 and GLUT4 genes to the susceptibility to type 2 (non-insulin-dependent) diabetes mellitus in different populations (1996)
    Springer
    Acta diabetologica 33 (1996), S. 193-197 
    Details
    ISSN: 1432-5233
    Keywords: Glucose transporter glycoproteins ; Non-insulin-dependent diabetes ; Genetic polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Polymorphic variation of genes encoding the glucose transporters glycoproteins (GLUT) may contribute to the genetic susceptibility to type 2 (non-insulin-dependent) diabetes. In this study we evaluated the allele and genotype frequencies of GLUT1 and GLUT4 restriction fragment length polymorphism (RFLP), revealed by digestion withXbaI for GLUT1 andKpnI for GLUT4, in Caucasian, Chinese, Japanese, Asian Indian and American black populations. No differences of theKpnI GLUT4 RFLP were found between control and diabetic subjects in any ethnic group or when all data are combined. In contrast, positive results were found for theXbaI RFLP: (1) most ethnic groups showed an association of allele 1 with type 2 diabetes, and this association was maintained when all groups were analysed together; (2) after stratifying for sex and obesity, this association was significant only for overweight/obese women. This joint analysis suggests that GLUT1 polymorphism may contribute to susceptibility to type 2 diabetes in some populations, and especially in overweight/obese women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02048542
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  • 5
    Electronic Resource
    Electronic Resource
    New HLA DNA polymorphisms associated with autoimmune diseases (1986)
    [s.l.] : Nature Publishing Group
    Nature 322 (1986), S. 64-67 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The HLA class II region is considered to consist of five a-chain genes and eight ft-chain genes; these are encoded in three subregions, HLA-DP, -DQ and -DR. The DR subregion contains one a-chain gene and three or four polymorphic fi-chain genes, while the DP and DQ subregions each have two a- and ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/322064a0
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  • 6
    Electronic Resource
    Electronic Resource
    A genetic study of retinopathy in South Indian Type 2 (non-insulin-dependent) diabetic patients (1991)
    Springer
    Diabetologia 34 (1991), S. 441-444 
    Details
    ISSN: 1432-0428
    Keywords: Retinopathy ; Type 2 (non-insulin-dependent) diabetes mellitus ; genetic markers ; immunoglobulin genes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Genetic marker studies in diabetic retinopathy are controversial and frequently complicated by possible independent associations of Type 1 (insulin-dependent) diabetes mellitus with the markers so far analysed. We have looked for associations of candidate genes with retinopathy in South Indian Type 2 (non-insulin-dependent) diabetic patients; patients were subdivided into those with exudative maculopathy (n=53), proliferative retinopathy (n=40) and patients free from diabetic retinopathy with a minimum disease duration of 15 years (n=45). DNA was extracted from blood samples and studied by Southern blot hybridisation techniques and the following probe enzyme combinations: HLA-DQB1; Taq 1, HLA-DQA1; Taq 1, HLA-DRA; Bgl II, insulin gene hypervariable region; Pvu II and the switch region of the immunoglobulin IgM heavy chain gene (Sμ); Sac I. Differences in genotype distributions between the study groups were only detected with the Sμ probe which detects polymorphism of both Sμ and Sα1 (the switch region of IgA). Two alleles of Sα1 were detected sized 7.4 kilobase and 6.9 kilobase. The frequency of 6.9 kilobase homozygotes was lower in proliferative retinopathy (19%) compared to patients free from diabetic retinopathy (54%, p=0.005) and exudative maculopathy (46%, p=0.03). This data suggests that there is a genetic predisposition to proliferative retinopathy in Type 2 (non-insulin-dependent) diabetes of South Indian origin and that this is determined by polymorphism of the heavy chain immunoglobulin genes located on chromosome 14.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403184
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  • 7
    Electronic Resource
    Electronic Resource
    Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians (1997)
    Springer
    Diabetologia 40 (1997), S. 971-975 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Vitamin D receptor ; genotype ; insulin-dependent diabetes ; genetic susceptibility ; South India.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vitamin D has important immunomodulatory properties and prevents development of diabetes mellitus in an animal model of insulin-dependent diabetes (IDDM). We have studied the vitamin D receptor locus as a candidate for genetic susceptibility to IDDM in Southern Indian families. We found evidence for an association of one particular vitamin D receptor allele with IDDM susceptibility in this community. Ninety-three South Indian families consisting of available parents and an affected offspring were genotyped for three vitamin D receptor polymorphisms using the restriction enzymes TaqI, ApaI and BsmI as well as an adjacent microsatellite located to 12q14 (D12S85). Transmission disequilibrium testing analysis was used to assess preferential transmission of polymorphic markers and haplotypes with IDDM. There was significant excess transmission of vitamin D receptor alleles containing the BsmI restriction site to affected offspring in these families (p = 0.016). No association was found between D12S85 and IDDM. This study suggests that a polymorphism within or close to the vitamin D receptor gene may modify susceptibility to IDDM in this ethnic group. [Diabetologia (1997) 40: 971–975]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050776
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  • 8
    Electronic Resource
    Electronic Resource
    Evidence that single nucleotide polymorphism in the uncoupling protein 3 (UCP3) gene influences fat distribution in women of European and Asian origin (2000)
    Springer
    Diabetologia 43 (2000), S. 1558-1564 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Uncoupling protein-3 ; Europeans ; South Indians ; family association ; fat distribution ; body mass index ; Type II diabetes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Uncoupling proteins are mitochondrial transmembrane carriers implicated in the regulation of energy balance. Dysfunction of UCP3 (the predominant uncoupling protein in skeletal muscle) might therefore be expected to reduce thermogenic capacity, alter energy homeostasis and influence predisposition to obesity and Type II (non-insulin-dependent) diabetes mellitus. A variant in the putative promoter region of UCP3 (–55 c→t) has recently been identified, and an association with obesity reported in French subjects. Our aim was to study the pathophysiological role of this variant in diabetes-related and obesity-related traits using two distinct ethnic populations. Methods. The –55 c→t variant was genotyped in 85 South Indian and 150 European parent-offspring trios ascertained through Type II diabetic probands and in 455 South Indian subjects initially recruited to an urban survey into the prevalence of diabetes. Results. In South Indian and European parent-offspring trios there was no preferential transmission of either allele at the –55 c→t polymorphism to diabetic offspring (South Indians, p = 0.60; Europeans, p = 0.15). When family members were analysed for intermediate traits, the t-allele was associated with increased waist-to-hip ratio but only in females (South Indian mothers p = 0.036, daughters p = 0.032: European mothers p = 0.037, daughters p = 0.14). These findings were replicated in South Indian females from the population-based survey (p = 0.039). Conclusion/interpretation. The consistent association between the t-allele at this locus and increased waist-to-hip ratio in women from three separate data sets indicates that variation at this polymorphism (or another locus with which it is in linkage disequilibrium) influences fat distribution but that this effect is restricted to females. [Diabetologia (2000) 43: 1558–1564]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051569
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  • 9
    Electronic Resource
    Electronic Resource
    Positive association in the absence of linkage suggests a minor role for the glucokinase gene in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus amongst South Indians (1993)
    Springer
    Diabetologia 36 (1993), S. 633-641 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin dependent) diabetes mellitus ; glucokinase ; genetics ; linkage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mutations of the glucokinase gene have been implicated in the development of glucose intolerance in pedigrees with maturity-onset diabetes of the young. However, the contribution of the glucokinase gene to the aetiology of common Type 2 (non-insulin-dependent) diabetes mellitus is uncertain. We have studied the role of the glucokinase gene in the pathogenesis of Type 2 diabetes in South Indians, using both population-association and linkage methodology. A pair of CA-repeat sequences (GCK(3′) and GCK(5′)) straddling the glucokinase gene were employed as markers, each subject being typed using the polymerase chain reaction and polyacrylamide gel electrophoresis. Comparisons of allele frequencies at these markers were made between 168 Type 2 diabetic subjects and 70 racially-matched control subjects. No differences in allele frequencies were apparent at the GCK(5′) marker; however, there were significant differences in allele frequencies at the GCK(3′) marker between the Type 2 diabetic subjects and control subjects (χ 2=11.6, df=3, p=0.009) with an increase of the z allele (78.0% vs 66.4%) and a decrease of the z+2 allele (13.7% vs 25.0%) amongst the diabetic subjects. Linkage between glucose intolerance and the glucokinase gene was studied in 53 nuclear pedigrees under a variety of genetic models. Linkage was excluded (lod score 〈−2) at a recombination fraction of zero under five of the ten models used and highly unlikely (−2 〈 lod score 〈−1) under the others. The combination of positive association and negative linkage suggests that glucokinase acts as a minor gene influencing the development of Type 2 diabetes within this population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404073
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  • 10
    Electronic Resource
    Electronic Resource
    The genetics of non-insulin-dependent diabetes mellitus: tools and aims (1994)
    Springer
    Diabetologia 37 (1994), S. 959-968 
    Details
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; genetics ; linkage analysis ; population association studies ; complex inheritance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400458
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