Genetic epidemiology of beta-thalassemia in the Maldives: 23 years of a beta-thalassemia screening program

•Screening one-third of Maldives for Beta-thalassemia.•Maldives has the highest beta-thalassemia carrier frequency in the world.•Endogamy and consanguineous marriage should be regulated in Maldives.•Maldives thalassemia problem needs the WHO attention. The Maldives is an archipelago of 407,660 people according to population census of 2014, made up of 20 atolls, which has one of the highest prevalence of β-thalassemia worldwide. However, there is a dearth of studies related to β-thalassemia in the Maldives; therefore, in this study, we aimed to investigate the genetic epidemiology of β-thalassemia in Maldives. Blood samples were collected from 110,504 participants (1992–2015). Hemoglobin and RBC indices were measured on automated hematology analyzers. The quantitation of hemoglobin, HbA2, Hb F, and other abnormal Hb variants were assessed by HPLC. Molecular analysis was performed for the most common mutations in Southeast Asia for only 874 individuals either heterozygous or homozygous for these mutations using reverse dot blot hybridization. We screened 110,504 individuals for β-thalassemia between 1992 and 2015, which is ~ 30% of the entire population. The β-thalassemia carrier frequency was estimated to be 16.2%. Molecular diagnosis of 874 β-thalassemia carriers/major was performed for the most common seven mutations in Southeast Asia; of these, 139 patients were diagnosed as β-thalassemia major. This analysis showed that the most common mutations were IVS1 + 5G > C, (678; 77.6%), followed by the CD 30 (136; 15.6%). The least frequent mutation was FS8/9, (1, 0.001%), followed by IVS1 + 1G > T and CD15 (2; 0.2%). The frequency of β-thalassemia varies significantly among the 20 different atolls in Maldives. This study is expected to improve genetic counseling, creating awareness, enhance premarital screening, and customize the prevention and treatment strategies based on the needs of each atoll.