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Background  Narcolepsy-cataplexy is characterized by excessive daytime sleepiness with recurrent episodes of irresistible sleep, cataplexy, hallucinations and sleep paralysis. Its aetiology is unknown, but it is positively associated with the human leukocyte antigens (HLA) in all studied populations. The purpose of the present study was to investigate the association of HLA class II  DRB1 / DQB1  alleles with narcolepsy-cataplexy in Mexican Mestizo patients.    Methods  This is a case-control study of consecutive patients and ethnically matched controls. We included 32 patients diagnosed with typical narcolepsy-cataplexy, of the National Institute of Neurology, of the Institute of Psychiatry and at the Center of Narcolepsy at Stanford University. As healthy controls, 203 Mexican Mestizos were included.  DRB1  alleles were identified using sequence based typing. A PCR-SSOP reverse dot blot was used for  DQB1  typing. Allele frequency was calculated by direct counting and the significance of the differences was assessed using the Yates Chi square. Odds ratio and confidence intervals were evaluated.    Results  HLA- DRB1 *1501 (OR = 8.2; pc < 0.0001) and  DQB1 *0602 (OR = 8.4; pc < 0.0001) were found positively associated with narcolepsy. When deleting  DQB1 *0602+ patients from the analysis,  DQB1 *0301 was also found increased (OR = 2.7; p = 0.035; pc = NS).  DQB1 *0602/ DQB1 *0301 genotype was present in 15.6% of the cases (OR = 11.5; p = 0.00035), conferring a high risk.  DRB1 *0407 (OR = 0.2; p = 0.016 pc = NS) and  DQB1 *0302(OR = 0.4; p = 0.017, pc = NS) were found decreased in the patients. The gender stratification analysis showed a higher risk in females carrying  DRB1 *1501 (OR = 15.8, pc < 0.0001) and  DQB1 *0602 (OR = 19.8, pc < 0.0001) than in males (OR = 5.0 for both alleles; p = 0.012, pc = NS for  DRB1  & p = 0.0012, pc = 0.017 for  DQB1 ). The susceptibility alleles found in Mexicans with narcolepsy are also present in Japanese and Caucasians;  DRB1 *04 linked protection has also been shown in Koreans. A stronger HLA association is suggested in females, in accordance with the sexual dimorphism claimed previously.    Conclusion  This knowledge may contribute to a better understanding of the disease pathogenesis in different populations. The evaluation of the risk to develop narcolepsy-cataplexy in carriers of the described alleles/genotypes may also be possible. A larger sample should be analysed in Mexican and in other Hispanic patients to confirm these results.

Association of narcolepsy-cataplexy with HLA-DRB1 and DQB1in Mexican patients: A relationship between HLA and gender is suggested