Objectives: Our objective was to study mannose binding protein (MBP) polymorphisms in exonic and promoter region and correlate associated infections and vasoocculsive (VOC) episodes, 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 sickle cell disease (SCD) patients as 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 (voluntary blood donors).
Results: The observed frequencies of MBL2 promoter polymorphism (-221, Y/X) were 44.4% and 20.5% for the heterozygous genotype Y/X and 3.2% and 2.2% for the homozygous (X/X) respectively between SCD patients and controls. MBL2 Exon1 gene mutations were 29.4% and 50% for the heterozygous genotype A/O and 5.9% and 6.8% respectively for the homozygous (O/O) genotype between SCD patients and controls. The distribution of variant MBL2 polymorphisms did not show any correlation in SCD patients with or without vasoocculsive crisis (VOC) attacks (p=0.162; OR-0.486; CI=0.177 -1.33), however, it was correlated with infections (p=0.0162; OR-3.55; CI 1.25-10.04).
Conclusions: Although the frequency of the genotypes and haplotypes of MBL2 in SCD patients did not differ from controls, overall in the SCD patient cohort the increased representation of variant alleles was significantly correlated with infections (p<0.05). However, these variant MBL2 polymorphisms did not seem to play a significant role in the VOC episodes in this SCD cohort.
Keywords: Mannose-binding lectin, polymorphism, promoter, Sickle cell disease, MBL2, MBP