The Organization of the γ-Glutamyl Transferase Genes and Other Low Copy Repeats in Human Chromosome 22q11

Collins, John; Mungall, Andrew J.; Badcock, K.; Fay, Joanne M.; Dunham, Ian

doi:10.1101/gr.7.5.522

Cited by 44 publications

(32 citation statements)

References 42 publications

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“…The gene transcription is controlled by multiple promoters. Related gene sequences that are either nonfunctional or represent pseudogenes are found in chromosomes 18,19, and 20 (6,7). The multiple promoters and the alternative splicing are responsible for diversity of molecular forms and tissue specificity.…”

Section: Background Informationmentioning

confidence: 99%

Gamma-glutamyl transferase and cardiovascular disease

Ndrepepa¹,

Kastrati²

2016

Ann. Transl. Med.

103

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Gamma-glutamyl transferase (GGT) is an enzyme located on the external surface of cellular membranes. GGT contributes in maintaining the physiological concentrations of cytoplasmic glutathione and cellular defense against oxidative stress via cleavage of extracellular glutathione and increased availability of amino acids for its intracellular synthesis. Increased GGT activity is a marker of antioxidant inadequacy and increased oxidative stress. Ample evidence suggests that elevated GGT activity is associated with increased risk of cardiovascular disease (CVD) such as coronary heart disease (CHD), stroke, arterial hypertension, heart failure, cardiac arrhythmias and all-cause and CVD-related mortality. The evidence is weaker for an association between elevated GGT activity and acute ischemic events and myocardial infarction. The risk for CVD or CVD-related mortality mediated by GGT may be explained by the close correlation of GGT with conventional CVD risk factors and various comorbidities, particularly non-alcoholic fatty liver disease, alcohol consumption, oxidative stress, metabolic syndrome, insulin resistance and systemic inflammation. The finding of GGT activity in atherosclerotic plaques and correlation of intra-plaque GGT activity with histological indexes of plaque instability may suggest a participation of GGT in the pathophysiology of CVD, particularly atherosclerosis. However, whether GGT has a direct role in the pathophysiology of CVD or it is an epiphenomenon of coexisting CVD risk factors or comorbidities remains unknown and Hill's criteria of causality relationship between GGT and CVD are not fulfilled. The exploration whether GGT provides prognostic information on top of the information provided by known cardiovascular risk factors regarding the CVD or CVD-related outcome and exploration of molecular mechanisms of GGT involvement in the pathophysiology of CVD and eventual use of interventions to reduce circulating GGT activity remain a duty of future studies.

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Section: Background Informationmentioning

confidence: 99%

Gamma-glutamyl transferase and cardiovascular disease

Ndrepepa¹,

Kastrati²

2016

Ann. Transl. Med.

103

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“…However, Pawlak et al (1988) showed that at least four genes containing GGT sequences were present in the human genome. These are located at band q11 on chromosome 22 (Morris et al, 1993;Collins et al, 1997). Recently, It has been reported that the human GGT was encoded by a multigene family including at least seven genes.…”

Section: Yardimci 2000)mentioning

confidence: 99%

Activity Determination, Kinetic Analyses and Isoenzyme Identification of Gamma Glutamyltransferase in Human Neutrophils

Şener¹,

Yardımcı²

2005

BMB Reports

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Gamma-glutamyltransferase (GGT, EC 2.3.2.2) which hydrolyzes glutathione (GSH), is required for the maintenance of normal intracellular GSH concentration. GGT is a membrane enzyme present in leukocytes and platelets. Its activity has also been observed in human neutrophils. In this study, GGT was purified from Triton X-100 solubilized neutrophils and its kinetic parameters were determined. For kinetic analyses of transpeptidation reaction, γ-glutamyl p-nitroanilide was used as the substrate and glycylglycine as the acceptor. Apparent K m values were determined as 1.8 mM for γ-glutamyl pnitroanilide and 16.9 mM for glycylglycine. The optimum pH of GGT activity was 8.2 and the optimum temperature was 37ºC. It had thermal stability with 58% relative activity at 56ºC for 30 min incubation. L-serine, in the presence of borate, was detected as the competetive inhibitor. Bromcresol green inhibited neutrophil GGT activity as a noncompetetive inhibitor. The neutrophils seem to contain only the isoenzyme that is present in platelets. We characterized the kinetic properties and compared the type of the isoenzyme of neutrophil GGT with platelet GGT via polyacrylamide gel electrophoresis (PAGE) under a standart set of conditions.

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“…A further advantage of 22qDS is the capability of molecular testing for the 22q11.2 deletion, both to identify this subgroup with elevated genetic risk for schizophrenia and to characterize the specific predisposing DNA alteration (primary genetic lesion). Chromosome 22 was the first chromosome to be "sequenced," and its interesting genomic structure [23,24] has intrigued researchers attempting to understand the non-Mendelian genetic mechanisms that may underlie the 22qDS phenotype.…”

Section: Research Advantagesmentioning

confidence: 99%

Schizophrenia and genetics: New insights

Bassett

Chow²,

Weksberg³

et al. 2002

Curr Psychiatry Rep

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There is consistent evidence that the principal etiology of schizophrenia involves predisposing genetic factors. Recent years have seen several new insights in the genetics of schizophrenia. Several chromosomal regions show significant evidence that they contain schizophrenia susceptibility genes. A clinically relevant genetic subtype of schizophrenia (22q deletion syndrome) has been identified. There is new evidence that spontaneous mutations may play a role. There are new recommendations for genetic counseling. The progress to date suggests that understanding of a neurodevelopmental pathway from genetic susceptibility to schizophrenia will soon be fundamentally altered by molecular genetic advances in this complex disease.

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The Organization of the γ-Glutamyl Transferase Genes and Other Low Copy Repeats in Human Chromosome 22q11

Cited by 44 publications

References 42 publications

Gamma-glutamyl transferase and cardiovascular disease

Gamma-glutamyl transferase and cardiovascular disease

Activity Determination, Kinetic Analyses and Isoenzyme Identification of Gamma Glutamyltransferase in Human Neutrophils

Schizophrenia and genetics: New insights

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