Molecular Epidemiological Analysis of α and β Thalassemiain Shantou City of Guangdong Province

Objective To investigate the gene frequency and the pattern of mutation of α-thalassemia (α-thal) and β-thalassemia (β-thal) in Shantou city. Method Cluster sampling was used in this study. A total of 1034 of neonatal cord blood samples were collected for a prevalence study of α-thal, and a total of 1572 samples of premarriage or pregnant women and their spouses were collected for a β-thal prevalence survey. All subjects included in this study were registered in Shantou city. A complete blood count as well as hemoglobin electrophoresis analysis was performed in all of samples for phenotyping of α and β-thals. Those with Hb Bart's for α-thal and those with both microcytosis (MCV≤80 fl) and elevated levels of HbA2 (≥3.5%) for β-thal were further studied by DNA analysis. The α-thal and β-thal chromosomes were determined by using gap-PCR and reverse dot blot (RDB) assays respectively in the positive samples with α-thal or β-thal determinants. Unknown positive samples were analyzed directly with DNA sequencing. In addition, -a3.7 and -a4.2 alleles were screened using gap-PCR in all cord blood samples. Result Of all 1034 cord blood samples, including 7 well-known α-globin genotypes and 1 unknown β-globin genotype, 58 samples with 59 alleles were detected. The carrier rate of α-thalassemia in Shantou population is 5.71% (59/1034). The frequency of each genotype of the 7 α-thalassemia mutations was calculated to be 48.3% for -a3.7/aa, 29.3% for --SEA/aa, 12.1% for -a4.2/aa, 3.5% for --THAI/aa, and 1.7% for each --SEA/--SEA, aCSa/aa, and a1CD118+TCA. Of all 1572 adult samples, including 5 well-known type of β-thalassemia mutation and 1 unknown type, 15 alleles were detected, and one of the samples was CD41/42 compounded with -a3.7. The carrier rate of β-thalassemia in Shantou population was 0.95% (15/1572). The gene frequency of the 5 β-thalassemia mutations was calculated to be 26.7% for IVS-2-654 and -28, 20.0% for CD41/42, 13.2% for CD17, and 6.7% for βECD26. Conclusion The prevalence, mutation spectrum and mutant allele constitution of α-thal and β-thal in Shantou population are studied. The results would be useful for genetic counseling and for the future design of project for the prevention of thalassemia based on a larger scale population screening in this area.