FH20 and LIPOchip for the diagnosis of Familial Hypercholesterolemia

Elucigene FH20 and LIPOchip for the diagnosis of familial hypercholesterolemia

Familial hypercholesterolaemia (FH) is an autosomal dominant-genetic condition causing a risk of premature coronary heart disease. In the UK, prevalence is estimated at 1 in 500, affecting around 100,000 people in England, around 6,000 in Wales and approximately 10,000 in Scotland. At least 85% of people with FH in the UK remain undiagnosed.

Current guidelines recommend DNA testing using comprehensive genetic analysis (CGA) by mutation screening of the low-density lipoprotein receptor (LDLR) gene, using sequencing and dosage analysis by multiplex ligation-dependent probe amplification (MLPA), and targeted testing for specific mutations in apolipoprotein B (ApoB) and protein convertase subtilisin/kexin (PCSK9). It has been suggested that use of assay systems targeted to detect the most common FH mutations in a population might either replace CGA, or be usefully used as a pre-screen to reduce the number of samples requiring the apparently more expensive CGA. Elucigene FH20 and LIPOchip are commercially available genetic tests, designed to detect mutations that are most frequent in a Caucasian population. This study showed that both tests are cost-effective relative simple LDL screening. However, comprehensive genetic analysis was found to generate greater QALY gains at a cost substantially less than £20,000 per QALY gained. CGA was thus found to be the preferred testing option, with a high probability of cost-effectiveness.

Outcome and Translation

Based on the results of this diagnostic accuracy review and health economic model, NICE have issued guidance not recommending the use of Elucigene FH20 and LIPOchip for the diagnosis of FH and the initiation of cascade testing of relatives. This recommendation was made on the basis that a more comprehensive test (CGA) can cost-effectively detect more at-risk cases than either of the candidate tests under consideration.

NICE, (2011) NICE diagnostics guidance 2: Elucigene FH20 and LIPOchip for the diagnosis of familial hypercholesterolaemia, Manchester: National Institute for Health and Clinical Excellence.

HERU researchers involved in this research project: Dwayne Boyers, Mary Kilonzo and Paul McNamee

External Collaborators: P Sharma, G Mowatt, C Boachie, F Stewart, (HSRU, University of Aberdeen); Z Miedzybrodzka (Molecular Biology, University of Aberdeen) and W Simpson (Clinical Biochemistry, University of Aberdeen)

Publications

Sharma, P., Boyers, D., Boachie, C., Stewart, F., Miedzybrodzka, Z., Simpson, W., Kilonzo, M., McNamee, P. and Mowatt, G. (2011) Elucigene FH20 and LIPOchip for the diagnosis of familial hypercholesterolemia. Final report to NICE diagnostic review committee.

Sharma, P., Boyers, D., Boachie, C., Stewart, F., Miedzybrodzka, Z., Simpson, W., Kilonzo, M., McNamee, P. and Mowatt, G. (2012) 'Elucigene FH20 and LIPOchip for the diagnosis of familial hypercholesterolaemia: a systematic review and economic evaluation', Health Technology Assessment, 16(17).

Miedzybrodzka, Z., Bell, C., Boyers, D., Brown, C., Kelly, K., Tennant, S., Walker, S., Finnie, R., van Mourik, M., Pearson, P., Slater, S., Berg, J., Hailey, H., Gregory, H. and Simpson, W. (2012) 'A nationwide screening programme for familial hypercholesterolaemia in Scotland using existing services', (Abstract from British Human Genetics Conference, 17-19 September 2012), Journal of Medical Genetics, 49(Supplement 1), S115.

Presentations

Sharma, P., Boyers, D., Boachie, C., Stewart, F., Miedzybrodzka, Z., Simpson, W., Kilonzo, M., McNamee, P. and Mowatt, G. (2011) 'Elucigene FH20 and LIPOchip for the diagnosis of familial hypercholesterolemia', NICE Diagnostic Review Committee, Manchester, June 2011.

Sharma, P., Boyers, D., Boachie, C., Stewart, F., Miedzybrodzka, Z., Simpson, W., Kilonzo, M., McNamee, P. and Mowatt, G. (2012) 'Elucigene FH20 and LIPOchip for the diagnosis of familial hypercholesterolemia - NICE diagnostic appraisal process', Scottish Lipids Forum, Dunkeld, November 2012.

Sharma, P., Boyers, D., Boachie, C., Miedzybrodzka, Z., Simpson, W., Kilonzo, M., McNamee, P., Stewart, F. and Mowatt, G. (2012) 'Elucigene and LIPOchip for the diagnosis of familial hypercholesterolemia', Health Technology Assessment International (HTAi), Bilbao, Spain, 25th-27th June 2012.

Sharma, P., Mowatt, G., Stewart, F., Boachie, C., Miedzybrodzka, Z., Simpson, W., Boyers, D., Kilonzo, M. and McNamee, P. (2013) 'Challenges in conducting a systematic review of diagnostic test accuracy of genetic test: an example of the genetic diagnosis of familial hypercholesterolaemia', 21st Cochrane Colloquium, Quebec, 19-23 September 2013.