This test may be vetted by a pathologist.
The clinical information for the test must be clearly written on the request form. If clinical information is not provided, or does not provide sufficient justification for the test, the test may be declined.
Declined tests :
If a test is declined, the specimen will be held for a reasonable period (usually 3 weeks but dependant on the stability of the sample). Medical practitioners seeking approval for a declined test should email the on-call Chemical Pathologist ( chemicalpathologist@adhb.govt.nz ) , giving the patient's name and NHI number and the clinical justification for the test. If unable to email, call the on-call Chemical Pathologist via Lablink (09-3078995) and identify yourself as a doctor.
Apolipoprotein E is a component of lipoproteins and mediates the uptake of VLDL and chylomicron remnant particles by the liver and other tissues.
There are 3 Apo E alleles, e2, e3 and e4. The commonest allelle is e3.
Lipoprotein disorders : Subjects with homozygous e2/e2 genotype have impaired uptake of lipoprotein remnants and in the presence of other environmental or genetic factors develop familial dysbetalipoproteinemia (Broad beta disease; type III hyperlipidaemia). This is a mixed hyperlipidaemia with high levels of both cholesterol and triglyceride. Lipoprotein electrophoresis typically shows a "broad beta" pattern due to intermediate density lipoprotein. This disorder is highly atherogenic, and is very responsive to dietary and lifestyle interventions.
Alzheimer's disease
(AD): The e4 allele is associated with AD, being found in 20%-30% of the general population and in 45%-60% of patients with AD. The homozygous genotype e4/e4 is found in 12%-15% of patients with AD, but in only 2%-3% of the general population. While not everyone homozygous for e4 develops dementia, having this genotype might increase the chance of AD developing at an earlier age. Approximately 30% of people homozygous for e4 develop AD. (1)
As there are no proven effective interventions for AD, there are important ethical considerations before offering apo E genotyping. Risk prediction in the absence of any effective intervention may cause harm to the patient as well as to their relatives.
Recommendations for apo E genotyping testing in Alzheimer's disease (ref 1)
- The use of APOE genotyping as an adjunct to conventional diagnostic measures is unknown and the data suggest that it has low sensitivity and specificity and is of little diagnostic value in an individual patient. It has low predictive value in asymptomatic individuals and its use in this situation should be discouraged, except in well-defined research protocols with appropriate institutional ethics approval.
- APOE genotyping should not be used as the sole diagnostic test in patients in whom AD is suspected on clinical grounds.
- APOE genotype testing should not be offered without adequate pre-test and post-test counselling, education and support in patients in whom AD is suspected on clinical grounds. Genetic testing should follow carer or patient consent.
- APOE genotype analysis should not be performed in asymptomatic individuals. This position is supported by a number of overseas consensus statements (2-6)
REFERENCES
- Genetic testing for Alzheimer's disease Peter K Panegyres, Jack Goldblatt, Ian Walpole, Carmela Connor, Toni Liebeck and Karen Harrop. MJA 2000; 172: 339-343American College of Medical Genetics and American Society of Human Genetics Working Group on APOE and Alzheimer Disease. Statement on use of apolipoprotein E testing for Alzheimer disease. JAMA 1995; 274: 1627-1629.
- McConnell LM, Koenig BA, Greely HT, Raffin TA, and Alzheimer Disease Working Group of the Stanford Programme in Genomics, Ethics and Society. Genetic testing and Alzheimer disease: Has the time come? Nature Medicine 1998; 4: 757-759.
- National Institute on Aging and Alzheimer's Association Working Group. Apolipoprotein E genotyping in Alzheimer's disease. Lancet 1996; 347: 1091-1095.
- Post SG, Whitehouse PJ, Binstock RH, et al. The clinical introduction of genetic testing for Alzheimer disease. JAMA 1997; 277: 832-836.
- Relkin NR, Kwon YJ, Tsai J, Gandy S. The National Institute on Aging/ Alzheimer's Association recommendations on the application of apolipoprotein E genotyping to Alzheimer's disease. Ann NY Acad Sci 1996; 802: 149-171.
Emails to chemicalpathologist@adhb.govt.nz will receive priority attention from the on-call chemical pathologist.
If the query concerns a specific patient please include the NHI number in your email.
If email is not a suitable option, please contact the on-call chemical pathologist via Lablink (Auckland City Hospital ext. 22000 or 09-3078995).
Individual chemical pathologists may be contacted but will not be available at all times.
After-hours : contact Lablink (Auckland City Hospital ext. 22000 or 09-3078995) or hospital operator for on duty staff after hours.
Dr Samarina Musaad (Clinical Lead) : SamarinaM@adhb.govt.nz ext. 22402
Dr Cam Kyle: CampbellK@adhb.govt.nz ext 22052
Dr Weldon Chiu: WeldonC@adhb.govt.nz ext. 23427
Dr Campbell Heron: CHeron@adhb.govt.nz ext. 23427
Dr Sakunthala Jayasinghe: Sakunthala@adhb.govt.nz ext. 23427