Prevalence and Diversity of Haplotypes of Sickle Cell Disease in the Eastern Province of Saudi Arabia

Abstract

Hb F modulates sickle cell disease. Five major haplotypes of the β-globin gene cluster are associated with sickle cell disease. In the Eastern Province of Saudi Arabia, the Arab-Indian (AI) is most common. Single nucleotide polymorphism (SNP) genotyping (rs3834466, rs28440105, rs10128556, and rs968857) was carried out by nuclease allelic discrimination assay with target-specific forward and reverse primers, TaqMan probes, labeled with VIC and FAM. In 778 patients with sickle cell disease from the Eastern Province, a haplotype was assigned to 90.9% of all samples; 9.1% were classified as compound heterozygotes for the AI and an atypical haplotype. The distribution of haplotypes for 746 Hb S (HBB: c.20A > T) homozygotes was: 614 AI/AI, nine SEN/SEN (Senegal), 42 SEN/AI, nine CAM/CAM (Cameroon), one CAR (Central African Republic)/BEN (Benin), 71 AI/atypical. In Hb S/β-thalassemia (Hb S/β-thal), the distribution of Hb S haplotypes was: 22 AI/AI, one CAM/CAM, four AI/SEN, five AI/atypical. Mean Hb F in the haplotypes was: AI/AI 16.6 ± 7.5%, CAM/CAM 8.0 ± 4.1%, SEN/SEN 11.0 ± 5.1%, SEN/AI 15.1 ± 4.6%, AI/atypical 16.2 ± 6.5%. The presence of the SEN and CAM haplotypes was unexpected due to the apparent homogeneity of the population of the Eastern Province. We have successfully classified sickle cell disease haplotypes using the relatively inexpensive TaqMan assay for the first time. In addition, we have previously shown that children with AI haplotype have Hb F of 30.0% and mild disease, while in our cohort of adult AI patients, which might be the largest yet reported, Hb F was about 16.6%.

Keywords:

• Anemia
• haplotypes
• Hb F
• sickle cell disease
• single nucleotide polymorphism

Acknowledgments

We would like to extend our thanks to Mr. Abdulrazag Al-Wabary, Mr. Hani Farhan, and Mr. Ibrahim Alsager, King Faisal University, Al-Ahssa, Saudi Arabia, for their technical support. The views expressed in this article are the views of the authors and the funder had no role in the design, collection, analysis, and interpretation of the data and writing of the manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported by King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia, grant number [12-MED2224-46].