Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria

Hayder A Giha; Amre Nasr; Mattias Ekström; Elisabeth Israelsson; Gishanthi Arambepola; David Arnot; Thor G Theander; Marita Troye-Blomberg; Klavs Berzins; Per Tornvall; Gehad ElGhazali

doi:10.2119/molmed.2009.00136

Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria

Hayder A Giha, Amre Nasr, Mattias Ekström, Elisabeth Israelsson, Gishanthi Arambepola, David Arnot, Thor G Theander, Marita Troye-Blomberg, Klavs Berzins, Per Tornvall, Gehad ElGhazali

10 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Molecular Medicine
Volume	16
Issue number	1-2
Pages (from-to)	27-33
Number of pages	6
ISSN	1076-1551
DOIs	https://doi.org/10.2119/molmed.2009.00136
Publication status	Published - Jan 2010

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Giha, H. A., Nasr, A., Ekström, M., Israelsson, E., Arambepola, G., Arnot, D., Theander, T. G., Troye-Blomberg, M., Berzins, K., Tornvall, P., & ElGhazali, G. (2010). Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria. Molecular Medicine, 16(1-2), 27-33. https://doi.org/10.2119/molmed.2009.00136

Giha, HA, Nasr, A, Ekström, M, Israelsson, E, Arambepola, G, Arnot, D, Theander, TG, Troye-Blomberg, M, Berzins, K, Tornvall, P & ElGhazali, G 2010, 'Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria', Molecular Medicine, vol. 16, no. 1-2, pp. 27-33. https://doi.org/10.2119/molmed.2009.00136

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title = "Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria",

abstract = "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.",

author = "Giha, {Hayder A} and Amre Nasr and Mattias Ekstr{\"o}m and Elisabeth Israelsson and Gishanthi Arambepola and David Arnot and Theander, {Thor G} and Marita Troye-Blomberg and Klavs Berzins and Per Tornvall and Gehad ElGhazali",

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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

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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.

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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 -

Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria

Abstract

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