The associations of SEA-alpha thalassemia 1, XmnI-Ggamma polymorphism and beta-globin gene mutations with the clinical severity of beta-thalassemia syndrome in northern Thailand.

BACKGROUND: At least three genetic factors including beta-thalassemia mutations, alpha-thalassemia, and XmnI-Ggamma polymorphism were shown to modify clinical symptoms in beta-thalassemia disease.
OBJECTIVE: To determine associations of beta-thalassemia mutations, SEA-alpha thalassemia 1, and XmnI-Ggamma polymorphism, and clinical severity of beta-thalassemia in northern Thailand. MATERIAL AND
METHOD: Thirty-two beta-thalassemia major and 28 beta-thalassemia intermedia attending the Thalassemia Clinic at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand were recruited The beta-globin gene mutations and SEA-alpha thalassemia 1 were determined by MS-PCR and Gap-PCR, respectively. The XmnI-Ggamma polymorphism was identified by RFLP analysis. Odds ratio was calculated to evaluate the associations of these three genetic factors and clinical symptoms.
RESULTS: Eight beta-globin gene mutations (both beta0 and beta+) were found Twenty-nine point one percent of the patients had at least one XmnI-Ggamma site (XmnI-Ggamma: +) and 4.1% of the patients were heterozygote for the SEA-alpha thalassemia 1. The beta-globin gene mutations showed maximal impact and the XmnI-Ggamma polymorphism had minimal influence on clinical severity in this cohort. The SEA-alpha thalassemia 1 had the least effect on the clinical severity due to its low prevalence in these patients.
CONCLUSION: Although these three genetic factors play roles in modifying clinical symptoms of beta-thalassemia, the beta-thalassemia mutations should be considered first, followed respectively by the XmnI-Ggamma polymorphism and the SEA-alpha thalassemia 1, in management and prenatal diagnosis of beta-thalassemia in northern Thailand.