Molecular Heterogeneity of Beta-Thalassemia in the United Arab Emirates

Abstract

Theβ-thalassemia alleles in 313 national patients of the United Arab Emirates (UAE) have been characterized using PCR-based DNA-diagnostic techniques including DNA sequencing. A total of 212 patients had homozygous β-thalassemia and the remaining 101 were compound heterozygotes. More than half of the patients were homozygous for the IVS-I-5 (G→C) mutation followed by the sickle cell gene. The latter accounted for 25% of the chromosomes. In terms of frequency, five β-thalassemia mutations; IVS-I-5 (G→C), βS, –25 bp del, Cd 8/9 (+G) and IVS-II-1 (G→A) accounted for 83% of the alleles. In addition, 427 expatriate patients were studied: 256 with homozygous β-thalassemia and 171 were compound heterozygotes. In both the UAE nationals and expatriates, the β-thalassemia mutations and their frequency followed a similar trend. Our results indicate that the frequency of β-globin gene defects including β-thalassemia, sickle cell gene (βS) and abnormal hemoglobins is significantly increased and poses a major public health problem in the UAE. The number of homozygous patients strongly suggests a high degree of consanguinity among the UAE nationals. With 50 different β-thalassemia alleles, UAE is arguably the most heterogeneous population in the world. The diversity of these mutations reflects the historical admixture of genes and their migration from different areas in the region. Our data strongly suggest the need for a comprehensive thalassemia control program and provides a basis for population screening, genetic counseling and prenatal diagnosis.

Mutations of a country: a mutation review of single gene disorders in the United Arab Emirates (UAE)

“…Haplotype studies showed that 68% of the SCD patients in the UAE were homozygous for the Saudi Arabian/Indian haplotype (31/31), whereas only 8% were homozygous for the Bantu haplotype (20/20), which signifies the African influence. No homozygous Benin (19/19) was observed [Baysal, 2001[Baysal, , 2005. Haplotype 31 was associated with elevated mean HbF levels, compared to the other two haplotypes.…”

United Arab Emirates: Communities and Community Genetics

“…There are no accurate data regarding the exact β-thalassaemia frequency in the country; nevertheless, between 1989 and 2003, more than 850 patients have been registered at the Dubai Genetic and Thalassemia Center [13]. However, DNA-based data indicate this number to be much higher when other emirates are taken into account.…”

“…Mutation analysis among UAE nationals and expatriate β-thalassaemia patients demonstrated that the UAE is the most heterogeneous β-thalassaemia population in the world, with 50 different mutations reported to date [13]. The most common mutation in the UAE is IVS-1-5 (G → C) which is known to exist at very high frequencies in the Indian subcontinent and among populations surrounding India, but not among the Middle East Arabs.…”

“…Its low frequency in Kuwait and high frequency in the UAE and Oman favours the speculation that the gene was introduced into the Arabian Peninsula across the Strait of Hormuz. This navigational route still constitutes a major trade link between the Indian subcontinent and the Gulf state [13]. …”

“…Table 2 shows the 11 most common mutations and their origin. It is apparent from molecular studies that gene flow and heterogeneity of β-thalassaemia mutations represent complex anthropological influences from the Eastern Mediterranean and Sub-Saharan regions, the Far East, India and East Africa, supporting the fact that the diversity of β-thalassaemia mutation reflects historical events and gene migration in the region [13]. …”