Feb. 27, 2000
Emmanuel Mignot, Chair
CALL FOR PARTICIPANTS
Rationale:
Narcolepsy is a sleep disorder tightly associated with HLA DQB1*0602, mostly in the context of the HLA DRB1*1501, DQA1*0102, DQB1*0602 haplotype. Recent data indicate that for many HLA associated disease, multiple HLA alleles and HLA complex polymorphisms influence disease predisposition. The aim of this component is to explore the possibility that HLA complex polymorphisms located outside the HLA DR and DQ region influence narcolepsy susceptibility.
To test this hypothesis we will:
1. Collect and identify 100-200 HLA DRB1, DQB1 and DQB1 matched controls and narcoleptic patients. These subjects will also be matched for ethnicity.
2. Collect and identify singleton narcolepsy families where one the parent is homozygous for HLA DRB1*1501, DQA1*0102, DQB1*0602.
3. Type these subjects for HLA DRB1, DQA1, DQB1, DPB1, A, B, C and for the following microsatellites: D6S291, DQCAR, D6S273, D6S265, D6S2222, D6S2223, D6S2239, D6S2235, MIB and 5 TNF alpha Single Nucleotide Polymorphisms (SNPs).
4. Compare allele frequencies for all these linked markers in narcoleptic versus HLA DRB1, DQA1 and DQB1 matched subjects.
5. Perform Transmission Disequilibrium Tests (TDT) in singleton families homozygous for the narcolepsy susceptibility haplotype to explore if specific linked alleles at the studied markers are preferentially transmitted in the context of particular HLA DR B1*1501, DQB1*0102, DQB1*0602 haplotype.
We hope this study will allow us to identify novel narcolepsy susceptibility polymorphisms.
Call for participating centers: Additional participating centers are needed to:
1. Identify and recruit narcolepsy singleton families (HLA typing not required). Our goal is to recruit 300 singleton families.
2. Assist in the typing of any of the loci mentioned above in these samples (microsatellite, SNPs or HLA class I and class II typing). We are especially looking for assistance in the area of HLA class I typing.
Inquiries should be directed to:
E. Mignot MD PhD, Director or M. Okun, Clinical coordinator
Stanford Center For Narcolepsy, 1201 Welch Road, Room-P112
Stanford CA 94305-5485 USA
Mignot@leland.stanford.edu or michele.okun@leland.stanford.edu
1-650-725-6512 (M. Okun)
