TY - JOUR
T1 - Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria
AU - Giha, Hayder A
AU - Nasr, Amre
AU - Ekström, Mattias
AU - Israelsson, Elisabeth
AU - Arambepola, Gishanthi
AU - Arnot, David
AU - Theander, Thor G
AU - Troye-Blomberg, Marita
AU - Berzins, Klavs
AU - Tornvall, Per
AU - ElGhazali, Gehad
PY - 2010/1
Y1 - 2010/1
N2 - The role of inflammation in malaria pathogenesis is not fully understood, although C-reactive protein (CRP) may have a negative influence on host immunity to infections. An upstream polymorphism, -286 (C > T > A), in the CRP gene is known to influence CRP levels. In this study, a cohort of 192 Sudanese donors, followed for malaria infection for 9 years, had their CRP -286 gene locus genotyped by pyrosequencing. The number of malaria episodes experienced by each individual over the study period was used as an index for malaria susceptibility. The prevalence of the CRP alleles A, C and T were 21%, 52% and 27%, respectively. Importantly, the A-allele, unlike the C- and T-alleles or CRP genotypes, was significantly associated with an increased number of malaria episodes, P = 0.007. The proportion of A-allele carriers among donors not known to have had malaria during the study period was 18%, whereas it was 43% and 63% among donors who had experienced 1-4 and ≥5 malaria episodes, respectively, over the same period (P = 0.002). Furthermore, the A-allele was associated with higher parasite counts. In conclusion, the CRP -286 A-allele was associated with an increased susceptibility to uncomplicated Plasmodium falciparum malaria.
AB - The role of inflammation in malaria pathogenesis is not fully understood, although C-reactive protein (CRP) may have a negative influence on host immunity to infections. An upstream polymorphism, -286 (C > T > A), in the CRP gene is known to influence CRP levels. In this study, a cohort of 192 Sudanese donors, followed for malaria infection for 9 years, had their CRP -286 gene locus genotyped by pyrosequencing. The number of malaria episodes experienced by each individual over the study period was used as an index for malaria susceptibility. The prevalence of the CRP alleles A, C and T were 21%, 52% and 27%, respectively. Importantly, the A-allele, unlike the C- and T-alleles or CRP genotypes, was significantly associated with an increased number of malaria episodes, P = 0.007. The proportion of A-allele carriers among donors not known to have had malaria during the study period was 18%, whereas it was 43% and 63% among donors who had experienced 1-4 and ≥5 malaria episodes, respectively, over the same period (P = 0.002). Furthermore, the A-allele was associated with higher parasite counts. In conclusion, the CRP -286 A-allele was associated with an increased susceptibility to uncomplicated Plasmodium falciparum malaria.
U2 - 10.2119/molmed.2009.00136
DO - 10.2119/molmed.2009.00136
M3 - Journal article
C2 - 19946607
SN - 1076-1551
VL - 16
SP - 27
EP - 33
JO - Molecular Medicine
JF - Molecular Medicine
IS - 1-2
ER -
