Narcolepsy
Narcolepsy is a neurological disorder with excessive daytime sleepiness as the main symptom. About 1 in 2,000 people in the United States has narcolepsy with cataplexy, a sudden loss of muscle tone upon experiencing certain emotions that may cause the person to collapse. Other common symptoms include sleep paralysis and hypnagogic hallucinations upon falling asleep or waking up.Wikipedia
Certain variations in the HLA complex are thought to increase the risk of an autoimmune response to the proteins hypocretin or orexin, which have roles in controlling appetite and sleep patterns. Narcolepsy is thought to be an autoimmune disease, and it is strongly associated with two HLA genotypes, HLA-DRB1*1501 and HLA-DQB1*0602. [16453205?dopt=Abstract PMID 16453205] The T allele of SNP rs3135388 is associated with HLA-DRB1*1501. There is also a reported 9-fold increased risk for narcolepsy among youth vaccinated with the H1N1 flu vaccine (Pandemrix).
In fact, [PMID 24381371] concludes that since HLA-DQB1*06:02 positive subjects are at 251-fold increase in risk for narcolepsy, and all recent cases of narcolepsy after H1N1 vaccination are positive for this allele, DQB1 genotyping may be relevant to public health policy.
SNPs outside the HLA region can also influence risk of narcolepsy, although few have been replicated:
- rs5770917 between the CPT1B and CHKB genes on chromosome 22
- rs1154155 in the TCRA (T-cell receptor alpha) locus
- rs2305795 in the P2RY11 gene (the G allele appears to lower the risk of narcolepsy [PMID 21170044])
- rs104894574 in the HCRT gene
- rs387906655 in the MOG gene
Narcolepsy has also been seen as a secondary issue in patients with cerebellar ataxia and deafness. In such patients, several mutations in the DNMT1 gene have been reported, including:
