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  • 1
    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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  • 2
    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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  • 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: 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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  • 4
    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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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    In Finland insulin gene region encoded susceptibility to IDDM exerts maximum effect when there is low HLA-DR associated risk (1995)
    Springer
    Diabetologia 38 (1995), S. 1223-1229 
    Details
    ISSN: 1432-0428
    Keywords: Insulin gene ; HLA ; haplotype ; genetic susceptibility ; insulin-dependent diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An association between insulin-dependent diabetes mellitus (IDDM) and polymorphisms of the insulin gene on chromosome 11p15 (INS) is a consistent finding in Europid populations. While one study suggested that the INS association is restricted to HLA-DR4-positive individuals, studies in other Europid populations have shown the disease-associated INS genotype to confer susceptibility independently of HLA-DR. We have investigated the role of INS in susceptibility to IDDM in Finland, which has the highest incidence of diabetes mellitus in the world, at two polymorphic restriction sites, 5′ and 3′ to the insulin gene. From the DiMe (Childhood Diabetes in Finland) Study we studied 154 diabetic children without regard to HLA-DR type; 108 DR4 positive/non-DR3 diabetic children; 39 DR3 positive/non-DR4 diabetic children; 30 DR4/DR3 positive diabetic children; 31 non-DR4/non-DR3 diabetic children; 96 matched DiMe control subjects and 86 other healthy, non-diabetic Finnish control subjects. We found an overall association between IDDM and INS in the high-risk Finnish population only with the 5′ polymorphism and identified an INS haplotype negatively associated with IDDM in Finland. However, among diabetic subjects with a reduced HLA-associated susceptibility (non-DR4/non-DR3) both 3′ and 5′ INS loci showed an association with IDDM (p values 0.02 and 0.0002, respectively). Thus, in the Finnish population insulin gene-encoded susceptibility to IDDM exerts a maximum effect in those with reduced HLA-associated risk.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00422373
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  • 7
    Electronic Resource
    Electronic Resource
    Insulin receptor substrate-1 gene mutations in NIDDM; implications for the study of polygenic disease (1995)
    Springer
    Diabetologia 38 (1995), S. 481-486 
    Details
    ISSN: 1432-0428
    Keywords: Key words Insulin receptor substrate-1 ; gene mutations ; non-insulin-dependent diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Variations in the coding regions of the insulin receptor substrate-1 (IRS-1) gene have recently been suggested to contribute to the susceptibility of non-insulin-dependent diabetes mellitus (NIDDM). The purpose of this study was to examine the role of the IRS-1 missense mutations at codons 972 (glycine to arginine) and 513 (alanine to proline) in two diverse populations from South India and Finland at high risk for NIDDM. DNA was amplified and digested with restriction enzymes BstN1 to detect the codon 972 mutation and Dra III to detect the codon 513 mutation. The codon 513 mutation was not found in the study subjects. The codon 972 mutation was present in 10.3 % of 126 middle-aged NIDDM subjects and 5.3 % of 95 matched control subjects in the South Indians (p = 0.17). In elderly Finnish subjects the frequency of the mutation was 7.5 % in 40 NIDDM subjects and 7 % in 42 matched control subjects. The frequency of codon 972 mutation in the South Indian NIDDM subjects was very similar to the two previously published studies in Danish and French subjects although each study individually fails to reach conventional levels of significance. The data from all four ethnic groups were analysed together after ascertaining that significant heterogeneity did not exist between the studies. Overall, the frequency of the codon 972 mutation is found in 10.7 % NIDDM subjects and 5.8 % control subjects (p = 0.02). These studies suggest that the codon 972 mutation of the IRS-1 gene might act as a susceptibility gene predisposing to NIDDM in certain ethnic groups. [Diabetologia (1995) 38: 481–486]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00410287
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  • 8
    Electronic Resource
    Electronic Resource
    The genetic predisposition to fibrocalculous pancreatic diabetes (1989)
    Springer
    Diabetologia 32 (1989), S. 45-51 
    Details
    ISSN: 1432-0428
    Keywords: Genetics ; insulin gene ; DQβ gene ; fibrocalculous pancreatic diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fibrocalculous pancreatic diabetes (previously known as tropical pancreatic diabetes) is a rare cause of diabetes confined to countries within the tropical belt. The aetiology of fibrocalculous pancreatic diabetes is thought to be environmental although the agent(s) is unknown. We have investigated a possible genetic basis of this disease by looking for restriction fragment length polymorphisms of genes implicated in the aetiology of diabetes mellitus. Seventy-six Dravidian patients with fibrocalculous pancreatic diabetes were studied, and the restriction fragment length polymorphisms obtained compared to racially matched control subjects (n=94), patients with Type 2 (non-insulin-dependent) diabetes (n=87) and Type 1 (insulin-dependent) diabetes (n=58). No association of fibrocalculous pancreatic diabetes was found with restriction fragment length polymorphisms of the insulin receptor gene. Although no association of fibrocalculous pancreatic diabetes was found with polymorphism of the HLA DRα/DQα/DXα genes, an association was found with the Taq 1 restriction fragment length polymorphisms of the DQβ gene (DQβ T2/T6 present in 39% of patients with fibrocalculous pancreatic diabetes compared to 19% in control subjects; p=0.01; corrected p value=0.04) which is similar to that found in Type 1 but not Type 2 diabetes. An association of fibrocalculous pancreatic diabetes was also found with the hypervariable region in the 5-prime flanking region of the insulin gene; 40% of patients possessed the class 3 allele compared to 9.5% of control subjects p=0.0001; corrected p value=0.0008). In Type 2 diabetes, similar results were obtained with 33% subjects possessing the class 3 allele (p value compared to control subjects=0.0005; corrected p value=0.004). This study suggests that fibrocalculous pancreatic diabetes has a genetic component in its aetiology. Furthermore, its origin might be related to an individual with part of the genetic predisposition to diabetes (Type 1 or Type 2) who additionally has evidence of chronic calcific pancreatitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265403
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  • 9
    Electronic Resource
    Electronic Resource
    In Finland insulin gene region encoded susceptibility to IDDM exerts maximum effect when there is low HLA-DR associated risk (1995)
    Springer
    Diabetologia 38 (1995), S. 1223-1229 
    Details
    ISSN: 1432-0428
    Keywords: Key words Insulin gene ; HLA ; haplotype ; genetic susceptibility ; insulin-dependent diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An association between insulin-dependent diabetes mellitus (IDDM) and polymorphisms of the insulin gene on chromosome 11p15 (INS) is a consistent finding in Europid populations. While one study suggested that the INS association is restricted to HLA-DR4-positive individuals, studies in other Europid populations have shown the disease-associated INS genotype to confer susceptibility independently of HLA-DR. We have investigated the role of INS in susceptibility to IDDM in Finland, which has the highest incidence of diabetes mellitus in the world, at two polymorphic restriction sites, 5′ and 3′ to the insulin gene. From the DiMe (Childhood Diabetes in Finland) Study we studied 154 diabetic children without regard to HLA-DR type; 108 DR4 positive/non-DR3 diabetic children; 39 DR3 positive/non-DR4 diabetic children; 30 DR4/DR3 positive diabetic children; 31 non-DR4/non-DR3 diabetic children; 96 matched DiMe control subjects and 86 other healthy, non-diabetic Finnish control subjects. We found an overall association between IDDM and INS in the high-risk Finnish population only with the 5′ polymorphism and identified an INS haplotype negatively associated with IDDM in Finland. However, among diabetic subjects with a reduced HLA-associated susceptibility (non-DR4/non-DR3) both 3′ and 5′ INS loci showed an association with IDDM (p values 0.02 and 0.0002, respectively). Thus, in the Finnish population insulin gene-encoded susceptibility to IDDM exerts a maximum effect in those with reduced HLA-associated risk. [Diabetologia (1995) 38: 1223–1229]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00422373
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  • 10
    Electronic Resource
    Electronic Resource
    HLA-A associations with IDDM — a case of numbers? (1995)
    Springer
    Diabetologia 38 (1995), S. 751-752 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401853
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