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

Carrier frequency of the beta(s) allele has been reported to be 0.19% in Mazandaran province, northern Iran. Haplotype analysis of the beta(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 beta(s) alleles in Mazandaran province. Capillary electrophoresis was carried out to detect individuals suspected to have beta(s) allele(s). DNA analysis (PCR-RFLP) was used for final confirmation. To identify 5' to 3' beta-globin gene cluster haplotypes associated with beta(s) alleles, family linkage analysis was applied. Six polymorphic sites (HincIl 5' to epsilon, XmnI 5' to (G)gamma, HindIII in (G)gamma, HindIII in (A)gamma, HincIl 3' to psi beta and AvaII in beta were investigated using the PCR-RFLP method. Five different haplotypes were linked to beta(s) alleles, while beta(A) alleles were associated with nine haplotypes. Among the beta(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)(rani polymorphism 5' to the (G)gamma 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 Ps allele in the northern region.