Identification of β-globin haplotypes linked to sickle hemoglobin (Hb S) alleles in Mazandaran province, Iran

抄録

Carrier frequency of the β^S allele has been reported to be 0.19% in Mazandaran province, northern Iran. Haplotype analysis of the β^S allele helps trace the origin of its encoded hemoglobin (Hb) variant, Hb S, in a region. The aim of this study was to investigate the haplotypes associated with β^S alleles in Mazandaran province. Capillary electrophoresis was carried out to detect individuals suspected to have a β^S allele(s). DNA analysis (PCR-RFLP) was used for final confirmation. To identify 5′ to 3′ β-globin gene cluster haplotypes associated with β^S alleles, family linkage analysis was applied. Six polymorphic sites (HincII 5′ to ε, XmnI 5′ to ^Gγ, HindIII in ^Gγ, HindIII in ^Aγ, HincII 3′ to ψβ and AvaII in β) were investigated using the PCR-RFLP method. Five different haplotypes were linked to β^S alleles, while β^A alleles were associated with nine haplotypes. Among the β^S alleles, 53.9% were associated with the Benin (----++) haplotype, and the Arab-Indian (+++-++) haplotype had the second-highest frequency (23%). Unlike southern provinces, where the Arab-Indian haplotype is prominent, the Benin haplotype is the most frequent haplotype in northern Iran, and this may represent a founder effect. Since the Benin haplotype does not carry the XmnI polymorphism 5′ to the ^Gγ gene, which is responsible for high expression of Hb F, a severe form of sickle cell disease can be anticipated in patients that are homozygous for the β^S allele in the northern region.