Association of the glutathione S-transferase omega-1 Ala140Asp polymorphism with cerebrovascular atherosclerosis and plaque-associated interleukin-1 alpha expression.

BACKGROUND AND PURPOSE: Glutathione S-transferase omega-1 is a multifunctional enzyme. The Asp/Asp genotype of the Ala140Asp polymorphism of the GSTO1 gene has been alleged to increase the risk of vascular dementia. The objective of this study is to address the question of whether common vessel disorders known to cause vascular dementia are modified in their severity by this polymorphism. METHODS: The severity and expansion of atherosclerosis in the circle of Willis vessels, cerebral small vessel disease, and cerebral amyloid angiopathy were studied in a sample of 79 autopsy cases. Genotyping of the GSTO1 Ala140Asp polymorphism as well as immunohistochemistry for glutathione S-transferase omega-1 was performed. RESULTS: Carriers of the GSTO1 Asp/Asp genotype presented with more severe and widespread atherosclerosis than noncarriers. However, there was no effect on small vessel disease expansion and cerebral amyloid angiopathy severity. Immunohistochemically, we detected interleukin-1 alpha expressing macrophages in the lipid core of atherosclerosis plaques exhibiting glutathione S-transferase omega-1-positive material. GSTO1 Asp/Asp carriers showed larger areas of atherosclerosis plaques containing interleukin-1 alpha-positive material than carriers of the GSTO1 Ala-allele. CONCLUSIONS: The GSTO1 Asp/Asp genotype presumably modulates the severity and expansion of atherosclerosis in the circle of Willis. The cellular colocalization of glutathione S-transferase omega-1 and interleukin-1 alpha suggests a functional interaction between both proteins which in part might explain the function of glutathione S-transferase omega-1 in the pathogenesis of cerebral atherosclerosis.

AB-QTL analysis in winter wheat: I. Synthetic hexaploid wheat (T. turgidum ssp. dicoccoides x T. tauschii) as a source of favourable alleles for milling and baking quality traits.

The advanced backcross QTL (AB-QTL) strategy was utilised to locate quantitative trait loci (QTLs) for baking quality traits in two BC(2)F(3) populations of winter wheat. The backcrosses are derived from two German winter wheat cultivars, Batis and Zentos, and two synthetic, hexaploid wheat accessions, Syn022 and Syn086. The synthetics originate from hybridisations of wild emmer (T. turgidum spp. dicoccoides) and T. tauschii, rather than from durum wheat and T. tauschii and thus allowed for the first time to test for exotic QTL effects on wheat genomes A and B in addition to genome D. The investigated quality traits comprised hectolitre weight, grain hardness, flour yield Type 550, falling number, grain protein content, sedimentation volume and baking volume. One hundred and forty-nine SSR markers were applied to genotype a total of 400 BC(2)F(3) lines. For QTL detection, a mixed-model ANOVA was conducted, including the effects DNA marker, BC(2)F(3) line, environment and marker x environment interaction. Overall 38 QTLs significant for a marker main effect were detected. The exotic allele improved trait performance at 14 QTLs (36.8%), while the elite genotype contributed the favourable effect at 24 QTLs (63.2%). The favourable exotic alleles were mainly associated with grain protein content, though the greatest improvement of trait performance due to the exotic alleles was achieved for the traits falling number and sedimentation volume. At the QTL on chromosome 4B the exotic allele increased the falling number by 19.6% and at the QTL on chromosome 6D the exotic allele led to an increase of the sedimentation volume by 21.7%. The results indicate that synthetic wheat derived from wild emmer x T. tauschii carries favourable QTL alleles for baking quality traits, which might be useful for breeding improved wheat varieties by marker-assisted selection.

Expression of alpha2-macroglobulin, neutrophil elastase, and interleukin-1alpha differs in early-stage and late-stage atherosclerotic lesions in the arteries of the circle of Willis.

Different types of atherosclerotic (AS) lesions can be distinguished histologically and represent different stages of AS plaque development. Late-stage lesions more frequently develop complications such as plaque rupture and thrombosis with vessel occlusion than early AS lesions. To clarify whether protective, destructive, and inflammatory proteins are differentially expressed in early-stage and late-stage AS plaques we examined the proteinase inhibitor alpha(2)-macroglobulin (A2M), the neutrophil elastase (NE)-an enzyme degrading elastin and collagen fibers-and the proinflammatory protein interleukin-1alpha (IL-1alpha) in all types of AS plaques in the arteries of the circle of Willis from 78 human autopsy cases of both genders (61-91 years of age). Paraffin sections of AS plaques were immunostained with antibodies directed against A2M, NE and IL-1alpha. In initial AS lesions A2M was found, whereas NE and IL-1alpha were absent. NE and IL-1alpha became detectable as soon as a significant number of macrophages occurred within AS lesions. With increasing histopathological type of AS lesions, a marked increase of the area of the plaque exhibiting NE and IL-1alpha was observed. The area which exhibits A2M in AS plaques, on the other hand, did not vary significantly between the different stages. Thus, our results indicate a disproportionately high increase of the destructive enzyme NE and the proinflammatory protein IL-1alpha in relation to A2M with the progression of the grade of AS lesions pointing to the transgression of the protective capacity of A2M by NE and IL-1alpha in late-stage plaques. Therefore, our findings support the hypothesis that NE-induced tissue damage in late-stage AS plaques contributes to the development of plaque rupture and subsequent thrombosis.