The haptoglobin 2-2 genotype is associated with a reduced incidence of Plasmodium falciparum malaria in children on the coast of Kenya.
BACKGROUND
Haptoglobin (Hp) genotype determines the efficiency of hemoglobin clearance after malaria-induced hemolysis and alters antioxidant and immune functions. The Hp2 allele is thought to have spread under strong selection pressure, but it is unclear whether this is due to protection from malaria or other diseases.


METHODS
We monitored the incidence of febrile malaria and other childhood illnesses with regard to Hp genotype in a prospective cohort of 312 Kenyan children during 558.3 child-years of follow-up. We also conducted 7 cross-sectional surveys to determine the prevalence of Plasmodium falciparum parasitemia.


RESULTS
The Hp2/2 genotype was associated with a 30% reduction in clinical malarial episodes (adjusted incidence rate ratio, 0.67; P=.008 for Hp2/2 vs. Hp1/1 and Hp2/1 combined). Protection increased with age; there was no protection in the first 2 years of life, 30% protection at > or = 2 years of age, and 50% protection from 4-10 years of age. Children with the Hp1/1 genotype had a significantly lower rate of nonmalarial fever (P=.001).


CONCLUSIONS
Balancing selection pressures may have influenced the spread of the Hp gene. Our observations suggest that the Hp2 allele may have spread as a result of protection from malaria, and the Hp1 allele may be sustained by protection from other infections.
Atkinson
Sarah H
SH
KEMRI/Wellcome Trust Programme, Centre of Geographic Medicine Research, Kilifi District Hospital, Kilifi, Kenya. satkinson@kilifi.kemri-wellcome.org
Mwangi
Tabitha W
TW
Uyoga
Sophie M
SM
Ogada
Edna
E
Macharia
Alex W
AW
Marsh
Kevin
K
Prentice
Andrew M
AM
Williams
Thomas N
TN
D017677:Age Distribution; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003906:Developing Countries; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D012044:Regression Analysis; D012720:Severity of Illness Index; D017678:Sex Distribution
C485359:HP protein, human; D006242:Haptoglobins