Genetic Susceptibility to Diabetes Mellitus: the Distribution of Properdin Factor B (Bf) and Glyoxalase (GLO) Phenotypes

Kirk, R. L.; Theophilus, J.; Whitehouse, S.; Court, John M.; Zimmet, Paul

doi:10.2337/diab.28.10.949

Cited by 32 publications

(11 citation statements)

References 5 publications

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“…Type 1 (insulin-dependent) diabetes mellitus has been shown to be associated with HLA, factor B (BI) and complement component C4 in various white populations [7,9,11,13,20,23]. With the exception of C4 similar findings have been reported for black Americans with Type i diabetes [5,17,19,25].…”

supporting

confidence: 68%

The complement component C4 in black Americans with Type 1 (insulin-dependent) diabetes mellitus

Budowle

Roseman

et al. 1984

Diabetologia

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Summary.The complement component C4 variants C4A4, C4B 4 and C4B Q0 were found to be significantly increased in 64black patients with Type 1 (insulin-dependent) diabetes compared with 169 black control subjects, yielding relative risks of 3.3, 2.9 and 3.4, respectively. The increased frequencies of C4B 4 and C4B Q0 in black Type 1 diabetic patients are similar to those found in Caucasoid Type 1 diabetic patients. The data suggest that Type 1 diabetes in black Americans may be partially due to admixture of genes from whites.

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supporting

confidence: 68%

The complement component C4 in black Americans with Type 1 (insulin-dependent) diabetes mellitus

Budowle

Roseman

et al. 1984

Diabetologia

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“…Other studies have not found changes in GLO 1-1 phenotype or GLO' allele frequency in insulindependent diabetic patients (Tokanaga et al, 1982;Kirk et al, 1985). For non-insulin-dependent diabetic patients, Kirk et al (1979) found an excess of GLO 2-2 phenotype and a deficiency of GLO 1-2 phenotype whereas other surveys (Kirk et al, 1985;McCann et al, 1981) produced no significant difference. However, more interestingly, insulin-dependent diabetic patients without clinical complications had a significant excess of the homozygote GLO 1-1 whereas patients with complications did not (McCann et al, 1981).…”

Section: Biological Effects Of Methylglyoxalmentioning

confidence: 88%

The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life

Thornalley

1990

Biochemical Journal

727

502

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“…This deviation from Hardy-Weinberg equilibrium, which has been also reported in other populations (43), suggests the existence of yet unknown selection forces. Of note, this SNP has also been associated with diseases leading to decreased life expectancy such as prostate cancer and diabetes (44)(45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Role for glyoxalase I in Alzheimer's disease

Chen

Wollmer

Hoerndli

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

146

101

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P301L mutant tau transgenic mice develop neurofibrillary tangles, a histopathologic hallmark of Alzheimer's disease and frontotemporal dementia (FTDP-17). To identify differentially expressed genes and to gain insight into pathogenic mechanisms, we performed a stringent analysis of the microarray dataset obtained with RNA from whole brains of P301L mutant mice and identified a single up-regulated gene, glyoxalase I. This enzyme plays a critical role in the detoxification of dicarbonyl compounds and thereby reduces the formation of advanced glycation end products. In situ hybridization analysis revealed expression of glyoxalase I in all brain areas analyzed, both in transgenic and control mice. However, levels of glyoxalase I protein were significantly elevated in P301L brains, as shown by Western blot analysis and immunohistochemistry. Moreover, a glyoxalase I-specific antiserum revealed many intensely stained flame-shaped neurons in Alzheimer's disease brain compared with brains from nondemented controls. In addition, we examined a single nucleotide polymorphism predicting a nonconservative amino acid substitution at position 111 (E111A) in ethnically independent populations. We identified significant and consistent deviations from HardyWeinberg equilibrium, which points to the presence of selection forces. The E111A single nucleotide polymorphism was not associated with the risk for Alzheimer's disease in the overall population. Together, our data demonstrate the potential of transcriptomics applied to animal models of human diseases. They suggest a previously unidentified role for glyoxalase I in neurodegenerative disease. A lzheimer's disease (AD) and frontotemporal dementia are common forms of age-related dementing diseases. They are characterized by proteinaceous aggregates, which are resistant to proteolysis due to conformational changes and posttranslational modifications such as hyperphosphorylation and glycation (1-4). In AD, these aggregates are ␤-amyloid plaques and neurofibrillary tangles (NFT). NFT formation, in the absence of overt amyloid plaques, is found in a group of neurodegenerative diseases, including frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) (5, 6). In affected cells, the microtubule-associated protein tau is abnormally phosphorylated and relocalized from axonal to somatodendritic compartments, where it accumulates in aggregates that eventually assemble into NFT (7). The identification of mutations in the tau gene in FTDP-17 established that dysfunction of tau in itself can lead to dementia (6).NFT formation has been reproduced in transgenic mice by expression of FTDP-17 mutant tau, both in neurons (8-12) and in glial cells (13)(14)(15). Moreover, intracerebral injection of ␤-amyloid fibrils caused significant increases of NFT in the amygdala of P301L (FTDP-17) mutant mice (16). A similar increase was achieved by crossing ␤-amyloid-producing amyloid precursor protein mutant mice with P301L mice (17).The pathologic similarities between the P301L transgenic ...

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Genetic Susceptibility to Diabetes Mellitus: the Distribution of Properdin Factor B (Bf) and Glyoxalase (GLO) Phenotypes

Cited by 32 publications

References 5 publications

The complement component C4 in black Americans with Type 1 (insulin-dependent) diabetes mellitus

The complement component C4 in black Americans with Type 1 (insulin-dependent) diabetes mellitus

The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life

Role for glyoxalase I in Alzheimer's disease

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