Extensive Polymorphisms in Saudi Beta Thalassaemia Patients

Arjumand S. Warsy¹, Mohsen A.F. ElHazmi², Abdul Kareem Al Momin⁴, Ali AlHazmi³ and Aamer Aleem⁴

1Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. 2Emeritus Professor, College of Medicine, and Ash Shura Council (Saudi Parliament) Saudi Arabia. 3College of Health Services, King Saud University, Riyadh, Saudi Arabia. 4 Department of Medicine, College of Medicine, Riyadh, Saudi Arabia.

DOI : http://dx.doi.org/10.13005/bbra/1103

ABSTRACT: Beta thalassaemias occur in certain parts of the World and constitute a major health problem due to the chronicity of the associated anaemic state. In the Arab World, b-thalassaemia has been reported in most of the countries, though variations are frequent in the gene frequency and in the nature of the mutations leading to the thalassaemic state. This genetic heterogeneity in Arabs is obvious, since almost fifty different mutations have been identified. Some of the frequent mutations in majority of the Arab countries include codon 39 (C > T), IVSI-110 (G > A), IVSI-1 (G > A), IVSI-6 (T > C), IVSII-1 (G >A), codon 5(-CT), and IVSI-5 (G > C). These mutations are also reported in the Saudis in homozygous, heterozygous and double heterozygous states, and are a cause of the clinical heterogeneity, the hallmark of the b-thalassaemic state. Other factors, both genetic and environmental, further add to this heterogeneity. In this study we investigated polymorphism in the b-globin chains of hemoglobin. The study group included 68 Saudi patients diagnosed as suffering from b-thalassemia. Blood was extracted by venepuncture in EDTA tubes and DNA was extracted. The DNA was amplified by polymerase chain reaction amplification of 12 fragments of the entire b-globin chains, followed by sequencing on an ABI genetic analyser. Seven polymorphic sites were identified, all in the IVS-II except one, which was in the exon 1 in the codon 2 (CD2). These were IVSII 74, IVS II 16, CD2, IVS II 81, IVS II 666, and IVS II 76, IVS II 224 and IVS II 26. Comparison of these results with those reported in literature showed that every population has its own specific polymorphic sites. Some sites occur at frequencies of >50% in the b thalassemia patients, while others occur at a lower frequencies. Some of these polymorphic sites have been considered as disease causing mutations. Those identified in Saudis in this study were reported in only a few studies reported in literature. This suggests that either these polymorphisms were absent from the population or that it was not investigated. Further studies, both functional and in silico to determine the role played by these polymorphic sites in the development of b thalassemia and how they influence the disease presentation in Saudis are required.

KEYWORDS:

b-thalassemia; polymorphism; SNP; abnormal hemoglobins; Saudi Arabia

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