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  • 1
    Electronic Resource
    Electronic Resource
    Positive association in the absence of linkage suggests a minor role for the glucokinase gene in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus amongst South Indians (1993)
    Springer
    Diabetologia 36 (1993), S. 633-641 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin dependent) diabetes mellitus ; glucokinase ; genetics ; linkage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mutations of the glucokinase gene have been implicated in the development of glucose intolerance in pedigrees with maturity-onset diabetes of the young. However, the contribution of the glucokinase gene to the aetiology of common Type 2 (non-insulin-dependent) diabetes mellitus is uncertain. We have studied the role of the glucokinase gene in the pathogenesis of Type 2 diabetes in South Indians, using both population-association and linkage methodology. A pair of CA-repeat sequences (GCK(3′) and GCK(5′)) straddling the glucokinase gene were employed as markers, each subject being typed using the polymerase chain reaction and polyacrylamide gel electrophoresis. Comparisons of allele frequencies at these markers were made between 168 Type 2 diabetic subjects and 70 racially-matched control subjects. No differences in allele frequencies were apparent at the GCK(5′) marker; however, there were significant differences in allele frequencies at the GCK(3′) marker between the Type 2 diabetic subjects and control subjects (χ 2=11.6, df=3, p=0.009) with an increase of the z allele (78.0% vs 66.4%) and a decrease of the z+2 allele (13.7% vs 25.0%) amongst the diabetic subjects. Linkage between glucose intolerance and the glucokinase gene was studied in 53 nuclear pedigrees under a variety of genetic models. Linkage was excluded (lod score 〈−2) at a recombination fraction of zero under five of the ten models used and highly unlikely (−2 〈 lod score 〈−1) under the others. The combination of positive association and negative linkage suggests that glucokinase acts as a minor gene influencing the development of Type 2 diabetes within this population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404073
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  • 2
    Electronic Resource
    Electronic Resource
    An uncoupling protein 2 gene variant is associated with a raised body mass index but not Type II diabetes (1999)
    Springer
    Diabetologia 42 (1999), S. 688-692 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Uncoupling protein genes ; obesity ; leptin ; polymorphism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Linkage between markers close to the uncoupling protein 2 and 3 genes (11q13) and resting metabolic rate and a pre-diabetic phenotype have been found. The syntenic region in mouse has been found to be linked to quantitative traits associated with obesity and diabetes. UCP2 and UCP3 could therefore have an important role in body weight regulation and susceptibility to diabetes. We investigated a recently identified variant of the UCP2 gene in exon 8 as a marker for glucose and weight homeostasis. Methods. Length variation of the UCP2 exon 8 variant was studied by the polymerase chain reaction and agarose gel electrophoresis. Sequence variants of the UCP3 gene were sought by semi-automated DNA sequencing. Results. In 453 South Indian subjects, we found an association in women between the UCP2 exon variant and body mass index (p = 0.018). These findings were replicated in a separate group of South Indian subjects (n = 143, p 〈 0.001) irrespective of sex. Although no association was found between the UCP2 exon 8 variant and overt obesity in British subjects, the UCP2 genotype of obese women (n = 83) correlated with fasting serum leptin concentration (p = 0.006) in the presence of extreme obesity. These observations could not be explained by tight linkage disequilibrium with a coding region variant in the region of the UCP3 gene of biological significance. Lastly, no association was found between UCP2 and Type II (non-insulin-dependent) diabetes using either a family based design (85 families) or case control study (normal glucose tolerance n = 335, impaired glucose tolerance n = 42, Type II diabetes n = 76). Conclusion/interpretation. We have described a UCP2 gene exon 8 variant that may affect susceptibility to weight gain by influencing regulation of leptin. [Diabetologia (1999) 42: 688–693]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051216
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  • 3
    Electronic Resource
    Electronic Resource
    Evidence that single nucleotide polymorphism in the uncoupling protein 3 (UCP3) gene influences fat distribution in women of European and Asian origin (2000)
    Springer
    Diabetologia 43 (2000), S. 1558-1564 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Uncoupling protein-3 ; Europeans ; South Indians ; family association ; fat distribution ; body mass index ; Type II diabetes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Uncoupling proteins are mitochondrial transmembrane carriers implicated in the regulation of energy balance. Dysfunction of UCP3 (the predominant uncoupling protein in skeletal muscle) might therefore be expected to reduce thermogenic capacity, alter energy homeostasis and influence predisposition to obesity and Type II (non-insulin-dependent) diabetes mellitus. A variant in the putative promoter region of UCP3 (–55 c→t) has recently been identified, and an association with obesity reported in French subjects. Our aim was to study the pathophysiological role of this variant in diabetes-related and obesity-related traits using two distinct ethnic populations. Methods. The –55 c→t variant was genotyped in 85 South Indian and 150 European parent-offspring trios ascertained through Type II diabetic probands and in 455 South Indian subjects initially recruited to an urban survey into the prevalence of diabetes. Results. In South Indian and European parent-offspring trios there was no preferential transmission of either allele at the –55 c→t polymorphism to diabetic offspring (South Indians, p = 0.60; Europeans, p = 0.15). When family members were analysed for intermediate traits, the t-allele was associated with increased waist-to-hip ratio but only in females (South Indian mothers p = 0.036, daughters p = 0.032: European mothers p = 0.037, daughters p = 0.14). These findings were replicated in South Indian females from the population-based survey (p = 0.039). Conclusion/interpretation. The consistent association between the t-allele at this locus and increased waist-to-hip ratio in women from three separate data sets indicates that variation at this polymorphism (or another locus with which it is in linkage disequilibrium) influences fat distribution but that this effect is restricted to females. [Diabetologia (2000) 43: 1558–1564]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051569
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  • 4
    Electronic Resource
    Electronic Resource
    A DR3-related DXα gene polymorphism strongly associates with insulin-dependent diabetes mellitus (1986)
    Springer
    Immunogenetics 23 (1986), S. 47-51 
    Details
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract HLA-DQα and HLA-DXα gene polymorphisms were analyzed by Southern blot techniques in 78 Caucasoid insulin-dependent diabetes mellitus (IDDM) subjects and 55 control subjects. Five restriction fragment length polymorphisms of the HLA-DQ α gene correlated with HLA-DR typing. Two allelic DX α-related gene fragments, of 2.1 kb (U) and 1.9 kb (L) in size were identified. Genotype frequencies in the IDDM group for UU, UL, and LL were 54%, 38.5%, and 7.5%, respectively, whereas the corresponding frequencies in the control group were 24%,40%, and 36% (P 〈 0.00005 for differences in genotype frequencies). The U allele was associated particularly with IDDM patients who were DR3, with healthy controls who were DR3, as well as with IDDM patients who were not DR3. Thus, if this DX α U allele is not the DR3-associated IDDM susceptibility gene, it is the closest marker hitherto studied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00376521
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of razoxane on metastases from colorectal cancer (1987)
    Springer
    Clinical & experimental metastasis 5 (1987), S. 3-8 
    Details
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract At a median follow-up of 5 years, adjuvant razoxane (125 mg b.d.) given 5 days/week indefinitely following resection of colorectal cancer provided no benefit in terms of survival or recurrence for Dukes' A or B patients when compared to untreated controls. However in Dukes' C patients this treatment reduced the recurrence rate (P=0·05) and possibly increased survival time (P=0·08). Analysis now of the development of metastases in this trial which entered 272 patients over 7 years shows that in the Dukes' C group the incidence of liver metastases in the razoxane-treated patients is only about half that of the untreated patients (18 per cent versus 34 per cent) and that the time to first appearance of the liver metastases is twice as long in the razoxane-treated group as it is in the untreated group (80 weeks versus 40 weeks). It is concluded that the benefit of adjuvant razoxane observed in the Dukes' C patients is due to the antimetastatic activity of the drug in reducing and slowing down the development of hepatic secondaries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00116620
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  • 6
    Electronic Resource
    Electronic Resource
    Adjuvant oral razoxane (ICRF-159) in resectable colorectal cancer (1982)
    Springer
    Cancer chemotherapy and pharmacology 8 (1982), S. 293-299 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary One hundred and seventy six patients (81 controls, 95 receiving treatment) have entered a prospective randomized tiral of long-term oral adjuvant razoxane (ICRF-159) following removal of a colorectal cancer. The median follow-up is 34 months. The treated patients in Dukes' groups B and C have a significantly longer disease-free interval than the control patients (P=0.01 ‘as randomized’ and P=0.004 ‘as treated’). The differences in survival for Dukes' groups B and C are not significant, although follow-up is short. In Dukes' groups B and C, however, 24 of 56 of the patients in the control group have died (43%), as against only 17 of 64 in the treatment group (27%). The treatment produces very few side-effects, is well tolerated by patients, and is taken orally.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00254053
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  • 7
    Electronic Resource
    Electronic Resource
    Adjuvant oral Razoxane (ICRF 159) in resectable colo-rectal cancer (1983)
    Springer
    Cancer chemotherapy and pharmacology 10 (1983), S. 228-229 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00255772
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  • 8
    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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