Impact of Mannose-Binding Protein Gene Polymorphisms in Omani Sickle Cell Disease Patients.

Objectives: Our aim was to study mannose-binding protein (MBP) polymorphisms in exonic and promoter region and correlate it with associated infections and vasoocculsive (VOC) episodes in sickle cell disease (SCD) patients since MBP plays an important role in innate immunity by activating the complement system.

Methods: We studied the genetic polymorphisms in the Exon 1 (alleles A/O) and promoter region (alleles Y/X; H/L, P/Q) of the MBL2 gene, in SCD patients as an increased incidence of infections is seen in these patients. A PCR-based, targeted genomic DNA sequencing of MBL2 was used to study 68 SCD Omani patients and 44 controls (healthy voluntary blood donors).

Warfarin pharmacogenetics: development of a dosing algorithm for Omani patients.

The objective of our present study was to develop a warfarin dosing algorithm for the Omani patients, as performances of warfarin dosing algorithms vary across populations with impact on the daily maintenance dose. We studied the functional polymorphisms of CYP2C9, CYP4F2 and VKORC1 genes to evaluate their impact on the warfarin maintenance dose in an admixed Omani patient cohort with Caucasian, African and Asian ancestries. We observed a 64-fold inter-patient variability for warfarin to achieve stable international normalized ratio in these patients.

Warfarin pharmacogenetics: polymorphisms of the CYP2C9, CYP4F2, and VKORC1 loci in a genetically admixed Omani population.

This is the first study to evaluate the spectrum and prevalence of dose-predictive genetic polymorphisms of the CYP2C9, CYP4F2 and VKORC1 loci together, in a geographically defined, ethnically admixed healthy adult Omani population sharing common lifestyle/environmental factors. Since the present-day Omani population is the result of an admixture of Caucasian, African and Asian ancestries, we compared the pharmacogenetic profile of these three loci in this population. Interestingly, the Omani pharmacogenetic profile, in terms of allele and genotype distribution, has values that are intermediate between Caucasians and African Americans, the African admixture further substantiated by the presence of the CYP2C9*8 allele.