Haplotype analysis of beta thalassemia patients in Western Iran

β-thalassemia (β-thal) is the most common single gene disorder in Iran. To determine the chromosomal background of beta thalassemia mutations in Western Iran we studied β-globin gene cluster haplotypes in 314 β-thal and 70 βA chromosomes with a Kurd ethnic background from the province of Kermanshah, Iran using PCR-RFLP. β-thal mutations were analyzed using PCR-ARMS, RFLP and direct genomic sequencing. Haplotypes were constructed by analyzing the pattern of seven restriction sites through the β-globin gene cluster. Haplotype I was the most prevalent haplotype (35.7%) among β-thal chromosomes followed by haplotype III (28.6%). βA chromosomes similar to β-thal chromosomes were linked to diverse haplotypes but predominantly with haplotype I (42.9%). The predominant IVSII-1 (G → A) mutation in this population (33%) was strongly linked to haplotype III (66.1%) but was also found on chromosomes with haplotypes I, II, V, X and atypical. The second prevalent mutation was CD8/9 + G (13.5%) and showed a strong association with haplotype I (96.4%) and a weak association with haplotype V (3.6%). Haplotype background for Kurdish mutations among our studied population was similar to those among Kurdish Jews and people of Kurdistan of Iran. Identification of the most common mutations on different haplotype backgrounds can be explained by a variety of gene conversion and recombination events.