ABSTRACT
HLA-B∗15:02 is known as a biomarker for carbamazepine (CBZ) induced Steven-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) in some Asian populations. Hence United States Federal Drug Administration (USFDA) recommends HLA-B∗15:02 screening for Asian and other populations with a high prevalence of HLA-B∗15:02, prior to the administration of carbamazepine. This study was conducted to estimate the prevalence of HLA-B∗15:02 in a cohort of Sri Lankans. We observed an overall prevalence of 4.3% (4/93) among 93 Sri Lankans comprising 32 Sinhalese, 30 Sri Lankan Tamils and 31 Moors. The allele was detected in 3 [9.3%; 3/32] Sinhalese, 0 [0%; 0/30] Sri Lankan Tamils and in 1 [3%; 1/31] Moor. The overall prevalence of HLA-B∗15:02 in this population was close to that of other populations where the USFDA has recommended HLA-B∗15:02 screening. A larger study is required to confirm these findings, especially among the Sinhalese where the frequency appears to be high.
Subject(s)
Carbamazepine/adverse effects , HLA-B15 Antigen/genetics , Population Groups , Stevens-Johnson Syndrome/genetics , Carbamazepine/administration & dosage , Cohort Studies , Gene Frequency , Genetic Predisposition to Disease , Genetic Testing , Humans , Polymorphism, Genetic , Risk , Sri Lanka , Stevens-Johnson Syndrome/etiology , United States , United States Food and Drug AdministrationABSTRACT
Prothrombin (F2) 20210G>A [rs1799963 G>A] mutation is a genetic variant which predisposes to inherited thrombophilia. Highest prevalence of this rare mutation has been reported among Caucasian and Mediterranean populations with thrombophilic conditions compared to healthy controls. It is absent or occurs in a very low frequency in both thrombophilic patients and healthy controls of most South Asian populations. A previous study has demonstrated that the mutant allele is absent among Sri Lankan healthy controls. This study was conducted to determine the prevalence of the F2 20210G>A mutation among Sri Lankan patients with thrombo-embolic disorders. F2 20210G>A mutation analysis was carried out on 825 patients. These included 374 with arterial thromboembolic disorders, 303 with venous thromboembolic disorders (VTE) and 148 with pregnancy related complications. Genotyping was done using polymerase chain reaction followed by restriction fragment length polymorphism. The overall prevalence of the individuals detected with the mutation was 0.8 % (7/825) with a mutant allele frequency of 0.4 % (7/1,650), and all were heterozygotes. Further classification according to the types of thrombotic events showed a prevalence of 0.5 % (2/374), 1.3 % (4/303), and 0.7 % (1/148) respectively, in the three groups with arterial thrombosis, VTE and pregnancy complications. The respective mutant allele frequencies in the three different groups were 0.3 % (2/748), 0.7 % (4/606) and 0.3 % (1/296). Although these figures are lower than that of Caucasian and Mediterranean populations, they are relatively higher compared to other South Asian populations. Therefore, the F2 20210G>A mutant allele is not entirely absent among Sri Lankan patients with thrombo-embolic disorders.