title: Impact of Mannose-Binding Protein Gene Polymorphisms in Omani Sickle Cell Disease Patients.
abstract: OBJECTIVE
  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).
  
  
  RESULTS
  In SCD patients, the frequency of the genotype related to the high production of MBL was 0.35 (YA/YA) and for intermediate/low production was 0.65 (YA/XA, XA/XA, YA/YO, XA/YO, YO/YO). The observed frequencies of MBL2 gene 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 gene polymorphisms did not show any correlation in SCD patients with or without VOC attacks (p=0.16; 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.
authors.affiliation: Departments of Child Health, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Mathew
authors.initials: M
authors.lastname: Zachariah
authors.affiliation: Departments of Haematology, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Shoaib
authors.initials: S
authors.lastname: Al Zadjali
authors.affiliation: Departments of Child Health, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Wafa
authors.initials: W
authors.lastname: Bashir
authors.affiliation: Departments of Haematology, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Rahma
authors.initials: R
authors.lastname: Al Ambusaidi
authors.affiliation: Departments of Haematology, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Rhea
authors.initials: R
authors.lastname: Misquith
authors.affiliation: Departments of Child Health, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Wali
authors.affiliation: Departments of Haematology, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Anil
authors.initials: A
authors.lastname: Pathare