Thai Sudden Unexplained Death Syndrome (Thai SUDS), or Lai-Tai, is a major health problem among rural residents of northeastern Thailand. The cause has been identified as a genetic disease. SUDS, a disorder found in Southeast Asia, is characterized by an abnormal electrocardiogram with ST-segment elevation in leads V1-V3, identical to that seen in Brugada Syndrome (Brugada Sign, BS) and sudden death due to ventricular fibrillation and cardiac arrest (represents an arrhythmogenic marker that identifies high-risk for SUDS). SUDS victims have a sleeping disorder (narcolepsy). The HLA-DR locus is tightly associated with narcoleptic Japanese patients and HLA-DR2, DQ haplotypes were also found in Oriental narcoleptic patients. These circumstances prompted us to study the association between the disease and HLA Class II by HLA DNA typing using a PCR-SSO method, with five Thai SUDS families (18 BS-positive subjects as the cases, and 27 BS-negatives as the controls). We found that the HLA-DRB1 *12021 allele was significantly increased in BS-positive subjects (p = 0.02; OR = 4.5), the same as the HLA-DRB1*12021-DQB1 *0301/09 haplotype (p = 0.01; OR = 7.95). Our data suggests that the HLA-DRB1* 12021 allele associated with BS and the HLA-DRB1*12021-DQB1 *0301/09 is a haplotype susceptible to arrhythmogenic markers that can identify a high risk for SUDS.