difference was 58%, which was not statistically signifi- cant. To the best of our knowledge, the present study is the first to systematically investigate interindividual seasonal variations of CRP in several large populations. In two studies, seasonal variation of CRP was investigated on an intraindividual basis. Woodhouse et al. (2) reported higher CRP concentrations in winter with a peak in March, and Crawford et al. (13 ) found a significant seasonal variation of CRP with a peak in late February. The lack of seasonal variability of CRP in the present study may be somewhat contradictory to a previous report from our group (8) and to others (2, 13), in which seasonal variations of a variety of acute-phase proteins, such as fibrinogen, PAI-1, plasminogen, and  1 -glycopro- tein, have been observed. However, in contrast to the major acute-phase reactant CRP, these coagulation pro- teins are not exclusively related to the acute-phase re- sponse. The predictive value of CRP for cardiovascular events has been consistently established in a variety of prospec- tive studies (3, 4), and highly sensitive assays for CRP are now widely available with low analytical variability. In a recently published study (14 ), Meier-Ewert et al. demon- strated that baseline CRP concentrations are not subject to time-of-day variation. In the present study, we found no convincing evidence for seasonal variation of CRP; thus there should be no concern about misclassification of participants in population studies and in clinical practice measured during various seasons. This work was supported by Medical Research Council Program Grant G97900510 (to M.B.). We thank Gerlinde Trischler for excellent technical assistance. References 1. Kloner RA, Poole WK, Perritt RL. When throughout the year is coronary death most likely to occur? A 12-year population-based analysis of more than 220 000 cases. Circulation 1999;100:1630 – 4. 2. Woodhouse PR, Khaw KT, Plummer M, Foley A, Meade TW. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet 1994;343:435–9. 3. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflamma- tion, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973–9. 4. Koenig W, Sund M, Fro ¨hlich M, Fischer H-G, Lo ¨wel H, Do ¨ring A, et al. C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men. Results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Dis- ease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999;99:237– 42. 5. Liuzzo G, Biasucci LM, Gallimore RL, Grillo RL, Pepys MB, Maseri A. The prognostic value of C-reactive protein in severe unstable angina. N Engl J Med 1994;331:417–24. 6. Vigushin DM, Pepys MB, Hawkins PN. Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. J Clin Invest 1993;91:1351–7. 7. Hutchinson WL, Koenig W, Fro ¨hlich M, Sund M, Lowe GDO, Pepys MB. Immunoradiometric assay of circulating C-reactive protein: age-related val- ues in the adult general population. Clin Chem 2000;46:934 – 8. 8. Fro ¨hlich M, Sund M, Russ S, Hoffmeister A, Fischer H-G, Hombach V, et al. Seasonal variations of rheological and hemostatic parameters and acute- phase reactants in young, healthy subjects. Arterioscler Thromb Vasc Biol 1997;17:2692–7. 9. WHO-MONICA-Project Principal Investigators. The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease). J Clin Epidemiol 1988;41:105–14. 10. Bothig S. WHO MONICA project: objectives and design. Int J Epidemiol 1989;18(Suppl 1):S29 –37. 11. Draper NR, Smith H. Applied regression analysis, 2nd ed. New York: Wiley, 1981. 12. SAS Institute Inc. SAS, Ver. 6.12. Cary, NC: SAS Institute Inc., 1997. 13. Crawford VL, Sweeney O, Coyle PV, Halliday IM, Stout RW. The relationship between increased fibrinogen and markers of infection: a comparison of seasonal cycles. Q J Med 2000;93:745–50. 14. Meier-Ewert HK, Ridker PM, Rifai N, Price N, Dinges DF, Mullington JM. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects. Clin Chem 2001;47:426 –30. Serum Vitamin E and Lipid-adjusted Vitamin E Assess- ment in Friedreich Ataxia Phenotype Patients and Un- affected Family Members, Moncef Feki, 1 Samir Belal, 2 Habib Feki, 3 Malek Souissi, 1 Mahbouba Frih-Ayed, 4 Naziha Kaabachi, 1 Fayc ¸al Hentati, 2 Mongi Ben Hamida, 2 and Abderra- ouf Mebazaa 1* ( 1 Laboratory of Biochemistry, Rabta Hospital, 1007 Tunis, Tunisia; 2 Service of Neurology, National Institute of Neurology, 1007 Tunis, Tunisia; 3 Service of Community Medicine and Epidemiology, Hedi Chaker Hospital, 3029 Sfax, Tunisia; 4 Service of Neurology, Fattouma Bourguiba Hospital, 5000 Monastir, Tunisia; * address correspondence to this author at: Labo- ratoire de Biochimie Clinique, Ho ˆ pital La Rabta, 1007 Eljabbari, Tunis, Tunisia; fax 216-71-570-506, e-mail abderraouf.mebazaa@rns.tn) Friedreich ataxia (FA) is an autosomal recessive spinocer- ebellar syndrome with onset before age 25, characterized by progressive cerebellar ataxia, dysarthria, areflexia, sensory loss in lower limbs, pyramidal weakness, and Babinski signs (1). It is caused by an intronic expanded unstable GAA repeat in the frataxin gene (2) located on chromosome 9q13-q21 (3). Investigating five Tunisian families with typical FA phenotype, Ben Hamida et al. (4) had excluded linkage to the locus of FA in two families and provided evidence for genetic heterogeneity of the disease. Patients belonging to families not linked to the locus of FA showed very low serum vitamin E (VE) with no evidence of lipid malabsorption. The role of VE in maintaining human nervous system function is established, and the role of VE deficiency in neurologic disorders of a--lipoproteinemia and biliary atresia is well accepted (5, 6). Several reports (4, 7, 8–10) have described patients with a progressive spinocerebel- lar syndrome associated with very low serum VE in the absence of fat malabsorption or a--lipoproteinemia. This disease, termed ataxia with VE deficiency (AVED), is inherited with an autosomal recessive pattern (3, 4). The abnormal gene was mapped to chromosome 8q (11 ) and identified as the gene encoding for -tocopherol transfer protein (-TTP) (12 ). Because it is difficult to distinguish on the basis of clinical features between AVED patients in whom VE supplementation may be beneficial (7, 13, 14) and those with classic FA, we assessed serum VE, total cholesterol (TC), and triglycerides (TGs) in our patients with FA clinical phenotype and their unaffected family members. Clinical Chemistry 48, No. 3, 2002 577 Downloaded from https://academic.oup.com/clinchem/article/48/3/577/5641602 by guest on 08 March 2023