About the Narcolepsy Test

What is the Narcolepsy (HLA-DQB1*06:02) Genotyping Test?

The Narcolepsy (HLA-DQB1*06:02) Genotyping test will conclusively determine whether you carry the HLA-DQB1*06:02 allele which is associated with an increased lifetime risk of developing narcolepsy.

What is the HLA-DQB1 Gene?

The HLA-DQB1 gene is one of more than 200 genes in the HLA gene family. HLA genes are clustered on chromosome 6 and encode components of the human leukocyte antigen (HLA) complex. The HLA complex is an important part of the immune system, helping distinguish between the body’s own proteins and foreign proteins from viruses and bacteria. The protein encoded by the HLA-DQB1 gene forms a complex with the protein encoded by the HLA-DQA1 gene. This complex displays foreign proteins to the immune system in order to trigger an immune response against the foreign invader.

Variation in the HLA-DQB1 Gene

HLA genes vary significantly between individuals and several hundred different versions (or alleles) of the HLA-DQB1 gene have been identified. Each allele is allocated a particular number (such as HLA-DQB1*06:02). Specific HLA-DQB1 alleles are associated with various health conditions. For example, DQB1*03:02 in combination with either DQA1*03:01 or DQA1*03:02 increases the risk of celiac disease.

The DQB1*06:02 allele is associated with a significantly increased risk of narcolepsy as 90-99% of people affected with narcolepsy carry one or two copies of this allele. Individuals who carry two copies of the DQB1*06:02 allele (homozygotes) have an even higher risk (2- to 5-fold increased risk) compared to heterozygotes who carry one copy of the DQB1*06:02 allele and one copy of an alternative DQB1 allele. The presence of this allele alone is not enough to cause health problems though, as there are many people (15-25% of the general population) who have this allele and never develop narcolepsy. This indicates that other genetic and environmental factors are required for the development of narcolepsy.

Another susceptibility allele that has been identified is DQB1*03:01, but this allele does not increase the risk as much as DQB1*06:02. Several protective alleles have also been identified in different populations, including DQB1*05:01, DQB1*06:01, DQB1*06:03, DQB1*02 and DQB1*06:09. There may also be some risk contribution from the DQA1 alleles that encode the other component of the DQA1 – DQB1 complex.

Test Specifications

Age Limit None. This test can be taken at any age. Collection Method Buccal swabs. The test kit contains buccal swabs and instructions for collecting a buccal swab sample from inside the mouth.

Specimen Requirements Four buccal swabs, rubbed inside the mouth against the cheek for 15 seconds.

Testing Time 1 – 2 weeks.

Testing Methodology Sequence Based Typing (SBT)

Sample Handling DNA test kits do not have an expiry date and can be used at any time. Once the DNA sample is collected, it must be returned to the laboratory for testing within three months of collection. No refrigeration is required. Store at room temperature.

Limitations It is important to remember that the presence of the HLA-DQB1*06:02 allele does not mean that an individual will definitely develop narcolepsy. The HLA-DQB1*06:02 allele does increase the risk but there are many individuals that have this allele and never develop narcolepsy. There are also people that do not have the HLA-DQB1*06:02 allele who develop the disease. Alleles other than HLA-DQB1*06:02 allele will not be identified. An increased risk of narcolepsy and an accurate diagnosis are also dependent on a variety of genetic and non-genetic factors that are not detected by this assay.

Next, Understanding Your Narcolepsy (HLA-DQB1*06:02) DNA Test Results »

Recommended Links: Andlauer O et al. (2012). Predictors of hypocretin (orexin) deficiency in narcolepsy without cataplexy. Sleep 35(9): 1247-1255F.

Chabas D et al. (2003). The Genetics of Narcolepsy. Annu. Rev. Genomics Hum. Genet. 4: 459-483.

Dauvilliers Y, Arnulf I, Mignot E. (2007). Narcolepsy with cataplexy. Lancet. 369(9560): 499-511.

Hallmayer J et al. (2009). Narcolepsy Is Strongly Associated with the T-Cell Receptor Alpha Locus. Nature Genetics. 41: 708-711.

Hor H et al. (2010). Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy. Nat Genet. 42(9): 786-9.

Mignot E et al. (1994). DQB1*0602 and DQB1*0102 (DQ1) are better markers than DR2 for narcolepsy in Caucasian and Black Americans. Sleep 17(8 Suppl): S60-67.

Mignot E et al. (2001). Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. Am J Hum Genet. 68(3): 686-99.

Norris J (2009). Gene Found in Sudden Sleep Disorder Implicates the Immune System. USCF News Center.

Study supports causal role in narcolepsy for common genetic variant (2014). American Academy of Sleep Medicine.

Tafti M et al. (2014). DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe. Sleep. 37(1): 19-25.