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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
    Synergistic effect of angiotensin II type 1 receptor genotype and poor glycaemic control on risk of nephropathy in IDDM (1997)
    Springer
    Diabetologia 40 (1997), S. 1293-1299 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; diabetic nephropathy ; angiotensin II receptor ; DNA polymorphisms ; genetics.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the contribution of polymorphisms in the angiotensin II type 1 receptor gene (AGTR1) to renal complications in an inception cohort of 152 insulin-dependent diabetic (IDDM) patients examined 15–21 years after diabetes onset. This nested case-control study included 79 normoalbuminuric control subjects and 73 cases with evidence of nephropathy ranging from microalbuminuria to overt proteinuria. Subjects were genotyped for two AGTR1 polymorphisms (T573→C and A1166→C), and an adjacent CA repeat microsatellite. Allele C1166 and the 140 bp allele of the microsatellite were more frequent among nephropathy cases than normoalbuminuric control subjects (0.322 vs 0.247, and 0.618 vs 0.521, respectively), but these differences were not statistically significant. Although not significant by themselves, the AGTR1 polymorphisms contributed significantly to the risk of diabetic nephropathy when accompanied by poor glycaemic control. Among patients with frequent severe hyperglycaemia during the first decade of diabetes, the relative risk of nephropathy among allele C1166 carriers was 12.1 (95 % CI: 3.7–39.8), whereas it was only 1.4 (95 % CI: 0.6–3.5) among allele A1166 homozygotes. The difference between relative risks was highly significant (χ 2 = 8.25, p = 0.004 with 1 df). A similar pattern of higher risk of microalbuminuria, specifically among those carriers of allele C1166 who had poor glycaemic control was also found in an independent study of a cross-sectional sample of 551 IDDM individuals, although the effect was smaller in magnitude. We conclude that DNA sequence differences in the AGTR1 gene may modify the noxious effects of hyperglycaemia on the kidney. Allele C1166 carriers might especially benefit from nephropathy prevention programmes. [Diabetologia (1997) 40: 1293–1299]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050823
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    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
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