Q J Med 2003; 96: 541-542
© 2003 Association of Physicians
Correspondence |
Apolipoprotein E genotypes in Chinese patients with Wilson’s disease
1Department of Neurobiology
School of Life Science
University of Science & Technology of China
Hefei
People’s Republic of China
2University Hospital
Anhui College of TCM
Hefei
People’s Republic of China
e-mail (Dr Zhou): xpw{at}mail.ustc.edu.cn
Sir,
The name Wilson’s disease (WD) derives from great work of the English specialist Wilson (1912).1 On the Chinese mainland, approximately 3000 WD in-patients have been institutionalized at the Anhui College of TCM.2 WD is due to mutations in the ATP7B gene, whose various defects cause accumulation of copper in the liver, brain, kidney, etc.3 ApoE genotypes containing the 
4 allele are generally over-represented in the neurodegenerative diseases. Schiefermeier et al.4 reported the effects of ApoE genotypes on WD, and found that onset was significantly delayed with ApoE3/3. We therefore determined ApoE genotypes in our Chinese patients with WD.
We studied a series of 32 Chinese WD in-patients aged 9–43 years (mean ± SD 17.50 ± 10.01 years), age of onset 9–27 years (mean ± SD 16.18 ± 3.75). WD was diagnosed by typical symptoms and biochemical indicators:1 plasma caeruloplasmin < 200 mg/l, serum copper < 10 µmol/l, 24-h urine copper excretion 
100 µg and/or liver copper concentrations > 250 µg/g. ApoE genotype was determined by PCR using the commercially ApoE amplification kit.
The WD genotypes found were: ApoE3/3, 71.87%; 3/4, 15.63%; 2/3, 12.50%; 2/2, , 2/4 and 4/4, 0%. Discounting the one patient with osseo-muscular symptoms, in patients with neurological symptoms, the ratio of ApoE3/3 to non-ApoE3/3 was 16:8 (66.6%), while in the hepatic patients, it was even higher at 6:1 (85.7%). Onset age in patients with ApoE3/3 was delayed significantly compared to those with non-ApoE3/3 (17.30 ± 2.74 years vs. 13.33 ± 4.69 years, t = 2.98, p < 0.01).
The frequency of ApoE3/3 in WD was not significantly different from that in controls (Table 1, 
2 = 0.10, p > 0.05); frequencies of ApoE3 and ApoE4 alleles in WD were also not significantly different from those in controls (2 = 0.31 and 0.15, respectively, both p > 0.05).
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In healthy populations, ApoE
3/3 is found at approximately 53.98% in Caucasians and 78.96% in Chinese, Japanese, and Indians.5 Some ethnic differences may be involved in the neurobiology of WD, with a higher prevalence in Japan, Israel, and China than in Europe, lower mean age of onset in Chinese than in Caucasian patients (16.18 years vs. 20.98 years4), and more frequent ApoE3/3 in Chinese than in Caucasian patients (71.87% vs. 59%). Our confirmation that ApoE3/3 in our patients correlated with later onset, as in Caucasian patients,4 supports the idea that ApoE3/3 is a protective factor. Supplementation with alpha-tocopherol may improve symptoms of WD.6 In WD patients, total cholesterol, LDL and alpha-tocopherol levels are significantly lower than in controls.7 ApoE3 protein acts as an antioxidant and enhances neuronal growth.4 In neurodegenerative diseases, the impacts of the different ApoE genotypes may result in differences in neuronal maintenance and repair.8
Nevertheless, it is unclear why Asians have a higher prevalence of ApoE3/3 but also higher prevalence and earlier onset of WD compared to Caucasians. It may be that ApoE3/3 provides only mild neuroprotection. Definition of WD onset is also sometimes difficult: the presymptomatic ‘cause-unknown’ purpura2 is usually identified only after explicit gut haemorrhage; the earlier-onset cases may be induced by some unusual event such as head trauma, or neural inflammation.
Finally, although ApoE4 has been often considered a risk factor in Alzheimer’s disease, we found no negative effect of ApoE4 in WD.
Acknowledgments
Many thanks to Professors Yang RM and Bronstein J for their help. This study was supported financially by the Educational Commission of Anhui (98JL092, Wang XP), and the Fund of Neurodegenerative Diseases from National Education Department of China (679#, Zhou JN).
References
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2. Wang XP. Wilson disease: asymptomatic or late-onset? Acta Neurol Scand 1996; 94:4212.[Medline]
3. Dahlman T, Hartvig P, Lofholm M, Nordlinder H, Loof L, Westermark. K. Long-term treatment of Wilson’s disease with triethylene tetramine dihydrochloride (trientine). Q J Med 1995; 88:60916.
4. Schiefermeier M, Kollegger H, Polli MC, et al. The impact of apolipoprotein E genotypes on age at onset of symptoms and phenotypic expression in Wilson’s disease. Brain 2000; 123:58590.
5. Henderson JN, Crook R, Crook J, et al. Apolipoprotein E4 and tau allele frequencies among Choctaw Indians. Neurosci Lett 2002; 324:77–9.[CrossRef][Web of Science][Medline]
6. von Herbay A, de Groot H, Hegi U, Stremmel W, Strohmeyer G, Sies HJ. Low vitamin E content in plasma of patients with alcoholic liver disease, hemochromatosis and Wilson's disease. J Hepatol 1994; 20:41–6.[CrossRef][Web of Science][Medline]
7. Rodo M, Czonkowska A, Pulawska M, Swiderska M, Tarnacka B, Wehr H. The level of serum lipids, vitamin E and low density lipoprotein oxidation in Wilson's disease patients. Eur J Neurol 2000; 7:491.[CrossRef][Medline]
8. Chapman J, Korczyn AD, Karussis DM, Michaelson DM. The effects of APOE genotype on age at onset and progression of neurodegenerative diseases. Neurology 2001; 57:14825.
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