HLA-DQB1*06:02

Researchers have identified changes in several genes that influence the risk of developing narcolepsy. The most well-studied of these genes is HLA-DQB1, which provides instructions for making part of a protein that plays an important role in the immune system. The HLA-DQB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). The HLA-DQB1 gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins.GHR

A variation of the HLA-DQB1 gene called HLA-DQB1*06:02 has been strongly associated with narcolepsy, particularly in people who also have cataplexy and a loss of hypocretins. This variant is quite common worldwide, though, even though narcolepsy is quite rare; the 1997 publication that reported the association with narcolepsy reported 24% of people in general were HLA-DQB1*06:02, while 40-60% of narcolepsy patients carried it (an odds ratio equivalent to about 2).[PMID 9456467] With narcolepsy prevalence estimated at 50 per 100,000 people, that implies that about 100 out of every 100,000 people carrying HLA-DQB1*06:02 will be diagnosed with narcolepsy.

In a different population study, of 160 Japanese patients with narcolepsy without cataplexy, frequencies of DQB1*06:02 were significantly higher in patients compared with controls (allele frequency: 16.6 vs. 7.8%, p=1.1×10e-7, OR 2.36; carrier frequency: 31.3 vs. 14.7%, P=7.6×10(-8), OR 2.64).[PMID 27081540]