ABSTRACT
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.
Subject(s)
Cause of Death , Death, Sudden, Cardiac/ethnology , Electrocardiography , Female , Gene Frequency , Genetic Predisposition to Disease , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Haplotypes , Humans , Male , Pedigree , Risk Assessment , ThailandABSTRACT
Paternal microdeletion of chromosome 15 at q11-q13 has been reported in 75% of Prader-Willi syndrome (PWS) patients in western countries. Diagnosis of PWS in Thailand is mainly based on clinical observation and, in some cases, confirmed by conventional cytogenetic analysis. Loss of a tiny segment in this region (microdeletion) has made it difficult to discriminate from the normal karyotype. An attempt to solve this problem has been made by using a high resolution chromosome culture. However, this method is a tedious and time-consuming technique which is suitable for only experienced cytogeneticists. We report molecular cytogenetic analysis for PWS in Thai patients using FISH in addition to standard GTG- banding chromosome analysis. Nine Thai patients clinically diagnosed or with a suspicion of PWS were investigated. The FISH probes consist of the region-specific probes (SNRPN or D15S10 probe) and two chromosome 15-specific control probes (D15Z1 centromeric and PML chromosome 15 long arm probe). Bright field and FISH programs of an automatic karyotyper were applied to facilitate the efficiency of the chromosome analysis. We found that 2 out of 9 patients showed a deletion at 15q11-q13 region by standard GTG chromosome analysis while 4 out of 9 patients showed a delation in this region by FISH. Consistent losing of SNRPN and D15S10 signals in FISH was observed in these patients. This forty-four per cent deletion is considerably lower than those reported from western countries. We propose that DNA methylation at SNRPN promoter as well as structural abnormalities in other chromosome regions might also play a role in the etiology of this disorder in Thais, which should be investigated further.