XmnI Polymorphism in Sickle Cell Disease in North Morocco

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Sickle cell disease (SCD) is a prevalent severe monogenic disorder globally.
• The -158 XmnI polymorphism (C>T) in the Gγ-globin gene promoter influences Gγ-globin gene expression, leading to increased fetal hemoglobin (Hb F) production and potentially reduced SCD severity.
• Understanding the frequency and impact of this polymorphism is crucial for managing SCD in diverse populations.

Purpose of the Study:

• To determine the frequency of the -158 XmnI polymorphism in North Moroccan patients with sickle cell mutations.
• To investigate the association between the XmnI polymorphism and Hb F levels.
• To assess the XmnI polymorphism's role as a potential modulator of SCD clinical severity in the studied population.

Main Methods:

• Recruitment of 308 subjects with sickle cell mutations and 160 healthy individuals from Larache, Morocco.
• Analysis of complete blood count and Hb F levels.
• Determination of XmnI polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and statistical analysis.

Main Results:

• The allelic frequency of the XmnI polymorphism in the North Moroccan population was estimated at 15.8%.
• Homozygous and heterozygous frequencies for the polymorphism were 7.6% and 16.4%, respectively.
• The polymorphism was present in 20.6% of SS patients, 24.2% of AS carriers, 28.6% of Hb S/β-thalassemia patients, and 22.5% of AA subjects, indicating a low overall frequency.

Conclusions:

• North Moroccan sickle cell disease patients exhibit a low frequency of the -158 XmnI polymorphism.
• This low frequency is associated with elevated Hb F levels.
• The findings suggest that the XmnI polymorphism, despite its low prevalence, plays a role in modulating SCD severity by influencing Hb F production in this population.