Impact of mannose-binding protein gene polymorphisms in omani sickle cell disease patients

Mathew Zachariah, Shoaib Al Zadjali, Wafa Bashir, Rahma Al Ambusaidi, Rhea Misquith, Yasser Wali, Anil Pathare

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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). 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.

Original languageEnglish
Article numbere2016013
JournalMediterranean Journal of Hematology and Infectious Diseases
Volume8
Issue number1
DOIs
Publication statusPublished - 2016

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Mannose-Binding Lectin
Sickle Cell Anemia
Genes
Genotype
Alleles
Infection
Genetic Promoter Regions
vif Genes
Genetic Polymorphisms
Blood Donors
DNA Sequence Analysis
Innate Immunity
Gene Frequency
Haplotypes
Exons

ASJC Scopus subject areas

  • Hematology
  • Infectious Diseases

Cite this

Impact of mannose-binding protein gene polymorphisms in omani sickle cell disease patients. / Zachariah, Mathew; Al Zadjali, Shoaib; Bashir, Wafa; Al Ambusaidi, Rahma; Misquith, Rhea; Wali, Yasser; Pathare, Anil.

In: Mediterranean Journal of Hematology and Infectious Diseases, Vol. 8, No. 1, e2016013, 2016.

Research output: Contribution to journalArticle

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title = "Impact of mannose-binding protein gene polymorphisms in omani sickle cell disease patients",
abstract = "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). 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.",
author = "Mathew Zachariah and {Al Zadjali}, Shoaib and Wafa Bashir and {Al Ambusaidi}, Rahma and Rhea Misquith and Yasser Wali and Anil Pathare",
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T1 - Impact of mannose-binding protein gene polymorphisms in omani sickle cell disease patients

AU - Zachariah, Mathew

AU - Al Zadjali, Shoaib

AU - Bashir, Wafa

AU - Al Ambusaidi, Rahma

AU - Misquith, Rhea

AU - Wali, Yasser

AU - Pathare, Anil

PY - 2016

Y1 - 2016

N2 - 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). 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.

AB - 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). 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.

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