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  • 1
    Electronic Resource
    Electronic Resource
    Diabetes susceptibility at IDDM2 cannot be positively mapped to the VNTR locus of the insulin gene (1996)
    Springer
    Diabetologia 39 (1996), S. 594-599 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; insulin gene ; tyrosine hydroxylase gene ; VNTR ; linkage disequilibrium.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An inconsistency has come to light between the conclusion of Lucassen et al. that IDDM2 (11p15.5) must lie within a 4.1 kilobase (kb) segment at the insulin (INS) locus and their own data showing statistically significant associations between insulin-dependent diabetes mellitus (IDDM) and markers beyond the boundaries of that segment. We present data from an independent study of 201 IDDM patients and 107 non-diabetic control subjects that also show significant association with a marker 5 ′ of the INS locus. Patients and control subjects were genotyped at INS/ + 1140 A/C (a surrogate for the variable number tandem repeat (VNTR) polymorphism in the regulatory part of the INS gene) and a marker 5 ′ of the tyrosine hydroxylase (TH) gene, TH/pINS500RsaI, making it 10 kb 5 ′ of the VNTR. Homozygotes for INS/ + 1140 allele ’ + ' were significantly more frequent among IDDM patients than among control subjects (73 vs 45 %, p 〈 0.001) giving an odds ratio of 3.3 (95 % confidence interval (CI): 2.0–5.3). A very similar association was found for homozygotes for the TH/RsaI allele ’ + ' (53 vs 31 %, p 〈 0.001) giving an odds ratio of 2.6 (95 %CI 1.6–4.2). By multilocus analysis, the TH/RsaI allele ’ + ' identified a subset of INS/ + 1140 alleles ’ + ' haplotypes that are more specifically associated with IDDM (odds ratio = 5.4, 95 %CI 2.9–10.4) than allele + 1140 ’ + ' as a whole. In conclusion, the segment of chromosome 11 that is associated with IDDM spans, at least, the INS and TH loci. No legitimate claim can be made that IDDM2 corresponds to the VNTR polymorphism at the INS locus until the correct boundaries for IDDM2 have been defined and other loci within them have been excluded as determinants of IDDM. [Diabetologia (1996) 39: 594–599]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403307
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Diabetes susceptibility at IDDM2 cannot be positively mapped to the VNTR locus of the insulin gene (1996)
    Springer
    Diabetologia 39 (1996), S. 594-599 
    Details
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; insulin gene ; tyrosine hydroxylase gene ; VNTR ; linkage disequilibrium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An inconsistency has come to light between the conclusion of Lucassen et al. that IDDM2 (11p15.5) must lie within a 4.1 kilobase (kb) segment at the insulin (INS) locus and their own data showing statistically significant associations between insulin-dependent diabetes mellitus (IDDM) and markers beyond the boundaries of that segment. We present data from an independent study of 201 IDDM patients and 107 non-diabetic control subjects that also show significant association with a marker 5′ of the INS locus. Patients and control subjects were genotyped at INS/+1140 A/C (a surrogate for the variable number tandem repeat (VNTR) polymorphism in the regulatory part of the INS gene) and a marker 5′ of the tyrosine hydroxylase (TH) gene, TH/pINS500-RsaI, making it 10 kb 5′ of the VNTR. Homozygotes for INS/+1140 allele ‘+’ were significantly more frequent among IDDM patients than among control subjects (73 vs 45%, p〈0.001) giving an odds ratio of 3.3 (95% confidence interval (CI): 2.0–5.3). A very similar association was found for homozygotes for the TH/RsaIallele ‘+’ (53 vs 31%, p〈0.001) giving an odds ratio of 2.6 (95% CI 1.6–4.2). By multilocus analysis, the TH/RsaI allele ‘+’ identified a subset of INS/+1140 alleles ‘+’ haplotypes that are more specifically associated with IDDM (odds ratio = 5.4, 95% CI 2.9–10.4) than allele +1140 ‘+’ as a whole. In conclusion, the segment of chromosome 11 that is associated with IDDM spans, at least, the INS and TH loci. No legitimate claim can be made that IDDM2 corresponds to the VNTR polymorphism at the INS locus until the correct boundaries for IDDM2 have been defined and other loci within them have been excluded as determinants of IDDM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403307
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Lipoprotein compositional abnormalities in type 1 (insulin-dependent) diabetic patients (1993)
    Springer
    Acta diabetologica 30 (1993), S. 11-16 
    Details
    ISSN: 1432-5233
    Keywords: Apoproteins ; Atherosclerosis ; Cholesterol ; Lipoproteins ; Triglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Patients with type 1 (insulin-dependent) diabetes mellitus in good metabolic control usually have normal plasma lipid levels yet they have an increased incidence of vascular complications. Abnormalities in the distribution and composition of lipoprotein subfractions might in part be responsible for the macroangiopathy seen in type 1 diabetes mellitus. The plasma lipids, lipoproteins and apolipoproteins were studied in 9 type 1 diabetic patients during conventional insulin therapy and in 14 healthy controls. Plasma lipoproteins were analysed by ultracentrifugation in a zonal rotor to evaluate their concentrations and flotation properties and for compositional analysis. In diabetic patients the mean glycosylated haemoglobin (HbA1c) was 9.44±1.02% and the plasma lipid concentrations were not significantly different from healthy controls. The very low density lipoprotein (VLDL) subclass cholesterol concentrations were no different in diabetic patients and control subjects, but the VLDL cholesterol/triglyceride ratio was significantly lower in diabetic patients than in control subjects (0.34±0.05 vs 0.85±0.14; p〈0.05). The flotation rate of LDL2, the major component of low density lipoprotein (LDL) was lower in the diabetic patients compared with the control subjects. The cholesterol concentrations of intermediate density lipoprotein and LDL3, the minor component of LDL, were significantly higher (0.17±0.03 and 0.83±0.14 mmol/l respectively) in diabetic patients than in control subjects (0.05±0.02 and 0.24±0.08 mmol/l). The flotation properties and cholesterol concentrations of the high density lipoprotein (HDL) subclass, and the protein-lipid composition of LDL2, HDL2 and HDL3, were no different in diabetic patients and control subjects. Diabetic patients had lower apoprotein AII and higher CII and E levels than control subjects. the plasma lipoproteins in type 1 diabetes mellitus are characterized by increased intermediate density lipoprotein and LDL3 concentrations and by abnormal LDL2 flotation properties. These lipoprotein abnormalities might have a role in atherogenesis in type 1 diabetic patients since similar alterations were associated in some recent epidemiological studies with an increased incidence of cardiovascular disease in non-diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00572867
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    Paper (German National Licenses)
    Fulltext
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