PMID- 19432958
OWN - NLM
STAT- MEDLINE
DCOM- 20090825
LR  - 20211020
IS  - 1475-2875 (Electronic)
IS  - 1475-2875 (Linking)
VI  - 8
DP  - 2009 May 11
TI  - Haplotype specific-sequencing reveals MBL2 association with asymptomatic 
      Plasmodium falciparum infection.
PG  - 97
LID - 10.1186/1475-2875-8-97 [doi]
AB  - BACKGROUND: Mannose binding lectin (MBL) has an important role in the activation 
      of the complement system and opsonization of pathogenic microorganisms. Frequent 
      polymorphisms found in the MBL2 gene affect the concentration and functionality 
      of the protein and are associated with enhanced susceptibility to severe malaria 
      in African children. Most MBL2 typing strategies were designed to the analysis of 
      selected variants, the significance of whole haplotypes is poorly known. In this 
      work, a new typing strategy was developed and validated in an association 
      analysis of MBL2 with adult asymptomatic infection. METHODS: MBL2 allele-specific 
      fragments of 144 healthy Gabonese adults were amplified by using 
      haplotype-specific sequencing (HSS), a new strategy that combines 
      sequence-specific PCR and sequence-based typing. The Gabonese were investigated 
      for the presence of Plasmodium falciparum parasitaemia by the amplification of 
      parasite genes, immunochromatographic antigen detection and microscopic analysis. 
      HSS results were also compared with a previously used real-time PCR (RT-PCR) 
      method in 72 Euro-Brazilians. RESULTS: Fourteen polymorphisms were identified 
      beside the commonly investigated promoter (H, L; X, Y; P, Q) and exon 1 (A, O; O 
      = B, C or D) variants. The MBL2*LYPA/LYPA genotype was associated with the 
      absence of asymptomatic infection (P = 0.017), whereas the MBL2*LYQC haplotype 
      and YA/YO + YO/YO genotypes were associated with positive parasite counts in 
      asymptomatic adults (P = 0.033 and 0.018, respectively). The associations were 
      specific to LYPA (identical to the reference sequence Y16577) and LYQC (Y16578) 
      and would not have been revealed by standard genotyping, as there was no 
      association with LYPA and LYQC haplotypes carrying new polymorphisms defined by 
      sequence-based typing. In contrast, HSS and RT-PCR produced very similar results 
      in the less diverse European-derived population. CONCLUSION: In this work, a new 
      typing strategy for a highly polymorphic gene was developed and validated 
      focusing on the asymptomatic status of P. falciparum-infected adults. In 
      populations with high nucleotide diversity, it allowed for the identification of 
      associations with fine-scaled haplotypes that would not have been found using 
      common typing techniques. In this preliminary study, MBL2 haplotypes or SNPs 
      linked to them were found associated with susceptibility to infection and 
      parasitaemia control of asymptomatic adults.
FAU - Boldt, Angelica B W
AU  - Boldt AB
AD  - Department of Parasitology, Institute of Tropical Medicine, University of 
      Tubingen, Wilhelmstrasse 27, 72074 Tubingen, Germany. 
      juergen.kun@uni-tuebingen.de
FAU - Messias-Reason, Iara J
AU  - Messias-Reason IJ
FAU - Lell, Bertrand
AU  - Lell B
FAU - Issifou, Saadou
AU  - Issifou S
FAU - Pedroso, Maria Lucia Alves
AU  - Pedroso ML
FAU - Kremsner, Peter G
AU  - Kremsner PG
FAU - Kun, Jurgen F J
AU  - Kun JF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20090511
PL  - England
TA  - Malar J
JT  - Malaria journal
JID - 101139802
RN  - 0 (MBL2 protein, human)
RN  - 0 (Mannose-Binding Lectin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alleles
MH  - Animals
MH  - Base Sequence
MH  - Brazil/epidemiology
MH  - Female
MH  - Gabon/epidemiology
MH  - Genetic Predisposition to Disease/*epidemiology
MH  - Genotype
MH  - Haplotypes/*genetics
MH  - Humans
MH  - Malaria, Falciparum/epidemiology/*genetics
MH  - Male
MH  - Mannose-Binding Lectin/*genetics
MH  - Middle Aged
MH  - Parasitemia
MH  - Plasmodium falciparum
MH  - Polymerase Chain Reaction/methods
MH  - *Polymorphism, Genetic
MH  - Promoter Regions, Genetic
MH  - Young Adult
PMC - PMC2689254
EDAT- 2009/05/13 09:00
MHDA- 2009/08/26 09:00
PMCR- 2009/05/11
CRDT- 2009/05/13 09:00
PHST- 2009/01/16 00:00 [received]
PHST- 2009/05/11 00:00 [accepted]
PHST- 2009/05/13 09:00 [entrez]
PHST- 2009/05/13 09:00 [pubmed]
PHST- 2009/08/26 09:00 [medline]
PHST- 2009/05/11 00:00 [pmc-release]
AID - 1475-2875-8-97 [pii]
AID - 10.1186/1475-2875-8-97 [doi]
PST - epublish
SO  - Malar J. 2009 May 11;8:97. doi: 10.1186/1475-2875-8-97.