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  • 1
    ISSN: 1432-5233
    Keywords: Angiotensinogen gene ; Insulin receptor gene ; Methods of molecular genetics ; Nephropathy in type 1 (insulin-dependent) diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently, evidence has accumulated that genetic factors may contribute to the development of diabetic nephropathy in patients with type 1 (insulin-dependent) diabetes mellitus. To identify variation at a gene locus, newly developed methods are introduced which employ denaturing gradient gel electrophoresis (DGGE) to study sequence differences in polymerase chain reaction (PCR)-amplified DNA fragments as well as in genomic DNA. These techniques are illustrated with studies of the angiotensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropathy, we found no DNA sequence difference in the part of the angiotensinogen gene coding for angiotensin I. We did find, however, different distributions of a DNA polymorphism detected with the probe corresponding to exons 7 and 8 of the insulin receptor gene inRsaI DGGE blots in a comparison of patients with slow and fast progressing nephropathy. The interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy. However, more clinical and epidemiological data are needed to find out how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with diabetic nephropathy must be collected so that genetic studies will be possible.
    Type of Medium: Electronic Resource
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  • 2
    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
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  • 3
    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
    Library Location Call Number Volume/Issue/Year Availability
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