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  • 1
    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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  • 2
    ISSN: 1432-0428
    Keywords: Diabetes ; retinopathy ; glomerulosclerosis ; microangiopathy ; plasma glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a multinational study, fasting plasma glucose values in 3583 diabetic patients, aged 34–56 years, were related to the characteristics of these subjects and to the presence and severity of microangiopathy as ascertained by standardised methods. The patients were from nine different populations and ranged in number from 193 to 686 per population (London, Warsaw, Berlin (FRG), New Delhi, Tokyo, Havana, Oklahoma Indians, Arizona Pima Indians, and a national sample in Switzerland). In the total group, mean fasting plasma glucose was 8.1 mmol/l for those on diet alone, 9.7 mmol/l for those on oral agents, and 12.7 mmol/l for insulin-treated patients, of whom 25% had values exceeding 16.5 mmol/l. Since many variables were measured in each patient, it was possible to take into account many confounding factors in evaluating the relationship of plasma glucose levels to retinopathy and nephropathy.
    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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