Letter to the editor Elevated γ-glutamyltransferase and erythrocyte sedimentation rate in ischemic stroke in discordant monozygotic twin study Dear editor, In order to investigate potential genetic causes for stroke, we carried out a detailed comparison of blood chemistries of a pair of 62-year-old female twins discordant for stroke. A coincidental finding of a rightsided intracavernous cerebral anaeurysm measuring 9 mm was made in the affected twin, prior to the stroke. This has been managed conservatively ever since. The blood samples were collected and processed in parallel and a total of 59 biochemical markers were analyzed (Table 1). The data were compared with the corresponding reference intervals for the age group. These values were mostly within the normal range and similar between the sisters as expected, with the Correspondence: Jamal Nasir*, Division of Biomedical Sciences, St. George’s University of London, London SW17 0RE, UK. E-mail: [email protected] Conflict of interest: The authors declare no conflict of interest. DOI: 10.1111/ijs.12440
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exception of marked elevation of γ-glutamyltransferase (GGT) and erythrocyte sedimentation rate (ESR) levels in the affected twin. We identified a greater than 10-fold increase in GGT (244 U/l vs. 23 U/l) and ESR (36 mm/h vs. 2 mm/h) levels in this individual. Analysis of her previous medical records indicated elevated levels of GGT (81 U/l) significantly above the normal range, 14 years prior to the onset of stroke. These values continued to increase up to when she had stroke and beyond. By contrast, GGT readings for the unaffected twin have been near constant over the same period, and always within the normal range. The medical notes also reveal significantly elevated ESR in the affected twin following the stroke. Unfortunately, no ESR readings are available prior to this period. We were able to exclude the possible effects of factors normally associated with an increase in GGT levels, including alcohol, smoking, and anticonvulsants since neither drinks appreciable and only the unaffected twin smokes; the affected twin had taken anticonvulsants during childhood but her GGT values are higher than those reported in studies showing the effect of anticonvulsants on GGT (1). GGT, a marker for oxidative stress, and an indicator of endothelial function, is known to play a role in the formation and rupture of plaques leading to atheroscle-
rosis (2–4). Screening patients at risk of ischemic stroke for GGT and ESR should be relatively inexpensive, and GGT inhibitors are readily available (5).
Nirmal Vadgama1,2, David Gaze1, Jacob Ranson1, John Hardy2, and Jamal Nasir1* 1
Division of Biomedical Sciences, St. George’s University of London, London, UK 2 Institute of Neurology, University College London, London, UK
References 1 Lippi G, Montagnana M, Salvagno GL, Guidi GC. Influence of stable, long-term treatment with phenobarbital on the activity of serum alanine aminotransferase and γ-glutamyltransferase. Br J Biomed Sci 2008; 65:132–5. 2 Franzini M, Corti A, Martinelli B et al. γ-glutamyltransferase activity in human atherosclerotic plaques–biochemical similarities with the circulating enzyme. Atherosclerosis 2009; 202:119–27. 3 Whitfield JB, Zhu G, Nestler JE, Heath AC, Martin NG. Genetic covariation between serum γ-glutamyltransferase activity and cardiovascular risk factors. Clin Chem 2002; 48:1426–31. 4 Yu C, Kastin AJ, Ding Y, Pan W. Gamma glutamyl transpeptidase is a dynamic indicator of endothelial response to stroke. Exp Neurol 2007; 203:116–22. 5 Whitfield JB. Serum γ-glutamyltransferase and risk of disease. Clin Chem 2007; 53:1–2.
© 2015 World Stroke Organization
Letter to the editor
N. Vadgama et al.
Table 1 A comparison of blood markers between monozygotic twins discordant for stroke Parameter Clinical biochemistry Glucose fluoride Sodium Potassium Chloride Bicarbonate Urea Creatinine (enzymatic method) Bilirubin Alanine transaminase Alkaline phosphatase Albumin Gamma GT Calcium Phosphate Adjusted calcium Creatine kinase Cholesterol Triglyceride Cholesterol HDL Cholesterol LDL (calc) Total cholesterol/HDL ratio Non HDL cholesterol C reactive protein Free T4 TSH Vitamin B12 Folate Serum hormones and natriuretic peptide Prolactin LH FSH Oestradiol Progesterone Testosterone Cardiac troponin I NT-pro BNP Hematology HB WBC Platelet MCV ESR Neutrophil Lymphocyte Monocyte Eosinophil Basophil HCT RBC MCH MCHC RDW LUC %Hypo RBC Hb (calc) MPXI CD4 CD3 TruCount CD4 TruCount CD8 TruCount TruCount Lymphs
Units
Unaffected
Affected
Reference interval
Fold difference
mmol/l mmol/l mmol/l mmol/l mmol/l mmol/l μmol/l μmol/l U/l U/l g/l IU/l mmol/l mmol/l mmol/l U/l mmol/l mmol/l mmol/l mmol/l
6·6 134 4·6 96 25 4·0 51 3 24 184 35 244 2·24 1·27 2·34 54 3·7 0·56 2·22 1·2 1·7 1·5 25·8 13·8 1·03 446 13·9
3·0–6·0 (fasting) 133–146 3·5–5·3 95–108 22–29 2·5–7·8 60–110 0–21 0–52 30–130 35–50 0–38 2·20–2·60 0·80–1·50 2·20–2·60 40–320 0·90–2·20 0·80–2·00 3·3–5·2
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exception of marked elevation of γ-glutamyltransferase (GGT) and erythrocyte sedimentation rate (ESR) levels in the affected twin. We identified a greater than 10-fold increase in GGT (244 U/l vs. 23 U/l) and ESR (36 mm/h vs. 2 mm/h) levels in this individual. Analysis of her previous medical records indicated elevated levels of GGT (81 U/l) significantly above the normal range, 14 years prior to the onset of stroke. These values continued to increase up to when she had stroke and beyond. By contrast, GGT readings for the unaffected twin have been near constant over the same period, and always within the normal range. The medical notes also reveal significantly elevated ESR in the affected twin following the stroke. Unfortunately, no ESR readings are available prior to this period. We were able to exclude the possible effects of factors normally associated with an increase in GGT levels, including alcohol, smoking, and anticonvulsants since neither drinks appreciable and only the unaffected twin smokes; the affected twin had taken anticonvulsants during childhood but her GGT values are higher than those reported in studies showing the effect of anticonvulsants on GGT (1). GGT, a marker for oxidative stress, and an indicator of endothelial function, is known to play a role in the formation and rupture of plaques leading to atheroscle-
rosis (2–4). Screening patients at risk of ischemic stroke for GGT and ESR should be relatively inexpensive, and GGT inhibitors are readily available (5).
Nirmal Vadgama1,2, David Gaze1, Jacob Ranson1, John Hardy2, and Jamal Nasir1* 1
Division of Biomedical Sciences, St. George’s University of London, London, UK 2 Institute of Neurology, University College London, London, UK
References 1 Lippi G, Montagnana M, Salvagno GL, Guidi GC. Influence of stable, long-term treatment with phenobarbital on the activity of serum alanine aminotransferase and γ-glutamyltransferase. Br J Biomed Sci 2008; 65:132–5. 2 Franzini M, Corti A, Martinelli B et al. γ-glutamyltransferase activity in human atherosclerotic plaques–biochemical similarities with the circulating enzyme. Atherosclerosis 2009; 202:119–27. 3 Whitfield JB, Zhu G, Nestler JE, Heath AC, Martin NG. Genetic covariation between serum γ-glutamyltransferase activity and cardiovascular risk factors. Clin Chem 2002; 48:1426–31. 4 Yu C, Kastin AJ, Ding Y, Pan W. Gamma glutamyl transpeptidase is a dynamic indicator of endothelial response to stroke. Exp Neurol 2007; 203:116–22. 5 Whitfield JB. Serum γ-glutamyltransferase and risk of disease. Clin Chem 2007; 53:1–2.
© 2015 World Stroke Organization
Letter to the editor
N. Vadgama et al.
Table 1 A comparison of blood markers between monozygotic twins discordant for stroke Parameter Clinical biochemistry Glucose fluoride Sodium Potassium Chloride Bicarbonate Urea Creatinine (enzymatic method) Bilirubin Alanine transaminase Alkaline phosphatase Albumin Gamma GT Calcium Phosphate Adjusted calcium Creatine kinase Cholesterol Triglyceride Cholesterol HDL Cholesterol LDL (calc) Total cholesterol/HDL ratio Non HDL cholesterol C reactive protein Free T4 TSH Vitamin B12 Folate Serum hormones and natriuretic peptide Prolactin LH FSH Oestradiol Progesterone Testosterone Cardiac troponin I NT-pro BNP Hematology HB WBC Platelet MCV ESR Neutrophil Lymphocyte Monocyte Eosinophil Basophil HCT RBC MCH MCHC RDW LUC %Hypo RBC Hb (calc) MPXI CD4 CD3 TruCount CD4 TruCount CD8 TruCount TruCount Lymphs
Units
Unaffected
Affected
Reference interval
Fold difference
mmol/l mmol/l mmol/l mmol/l mmol/l mmol/l μmol/l μmol/l U/l U/l g/l IU/l mmol/l mmol/l mmol/l U/l mmol/l mmol/l mmol/l mmol/l
6·6 134 4·6 96 25 4·0 51 3 24 184 35 244 2·24 1·27 2·34 54 3·7 0·56 2·22 1·2 1·7 1·5 25·8 13·8 1·03 446 13·9
3·0–6·0 (fasting) 133–146 3·5–5·3 95–108 22–29 2·5–7·8 60–110 0–21 0–52 30–130 35–50 0–38 2·20–2·60 0·80–1·50 2·20–2·60 40–320 0·90–2·20 0·80–2·00 3·3–5·2
