Muhammad Abdul Naeem, Masood Anwar, Tahir Aziz Ahmad, Sabeen Khurshid.
Is beta thalassemia imported from the Mediterranean to the Subcontinent?.
Pak J Pathol Jan ;16(4):114-7.

Objective: The study was conducted to determine the source of beta thalassaemia mutations in Pakistan with the help of tracing the HLA antigens and common mutations. Material and Methods: A total of one hundred and fifty five subjects (n=155) were included in the study. It included fifty-four patients of thalassaemia major (n=54) and their one hundred and one (n=101) siblings. HLA typing by lymphocytotoxicity method was performed for HLA class I antigens. Retrospective analysis was carried out for common beta thalassaemia associated mutations. The most frequent HLA class I frequencies and beta thalassaemia mutations were compared with different populations of the world to establish genetic ancestry of our patients. Results: Our analyses showed that HLA B35 was present in our thalassaemics in the highest frequency. The antigen frequency (af) of HLA-B35 was 0.37 in thalassaemics while it was 0.21 in normal population (p=0.004). The af of HLA-B35 was 0.24 in siblings of thalassaemics (p=0.06) versus normal population. However, increased expression of HLA B35 has not been reported in a number of the thalassaemic populations studied for HLA antigen. The combined HLA class I frequencies for our population have the closest match with those found in Caucasian population of the Mediterranean region. The study of the mutations for beta thalassaemia shows the mutation Fr 8/9 (G+) to be present in the highest frequency in areas of northern Pakistan. The HLA and mutation analysis show a trend for this mutation to be Asian-Indian in origin. The other common beta thalassaemia mutation that is prevalent in Southern region of Pakistan is IVS-I-5 substantiated by HLA and mutation analysis studies. It is probably of Arabic decent, as it occurs along the seashore of old trade route extending from Yemen to Philippines. Conclusion: There is evidence that beta thalassaemia mutations arose denovo spontaneously in Pakistan and India and then spread within pedigrees. However there is a chance that IVI-I-5 mutation may have been imported from Arabic Peninsula. It will be interesting to study HLA frequencies / RFLPs of Sindhi and Baluch populations and compare them with seashore areas enroute.

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