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Genomics Day 2005: Genomics Day 2005: Public Health Genomics at CDC

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Group 1: Genetics and Immunity

The impact of Fc receptor IIa for IgG (FcyIIa) polymorphism on malaria and HIV susceptibility in western Kenya
Brouwer KC¹, Lal RB¹, Mirel LB¹, Yang C¹, Van Eijk A², Ayisi J², Otieno J³, Nahlen BL⁴, Steketee R¹, Lal A¹, and Shi YP¹.
(1) NCID, CDC
(2) Center for Vector Biology and Control Research, Kenya Medical Research Institute, Kisumu, Kenya
(3) New Nyanza Provincial General Hospital, Ministry of Health, Kisumu, Kenya,
(4) Roll Back Malaria Program, World Health Organization, Geneva, Switzerland

Genetic polymorphism of the Fc?IIa receptor on leukocytes determines IgG subclass binding. The histidine-131 variant leads to a receptor with high affinity for human IgG2, whereas the arginine allelic variant binds to IgG1 and IgG3 but poorly to IgG2. Considerable differences in the distribution of the Fc?RIIa polymorphism among ethnic groups have been reported, and this polymorphism has been found to play an important role in autoimmune diseases, especially SLE and infections due to encapsulated bacteria. The current study was undertaken 1) to examine the relationship between Fc?RIIa polymorphism and placental malaria (PM) infection in pregnant women of known HIV-1 serostatus, and 2) to evaluate the effect of polymorphism of the Fc?RIIa on perinatal HIV-1 transmission and HIV-positive child all-cause mortality. Fc?RIIa genotype was determined in 903 mothers and 448 pairs of HIV-seropositive mothers and their infants from a cohort study designed to assess the effect of placental malaria on HIV vertical transmission conducted from 1996 to 2001 in western Kenya . Fc?RIIa polymorphism was analyzed for associations with susceptibility to PM, perinatal HIV infection, all-cause child mortality in HIV-positive children. This study suggests that the IgG2-binding Fc?RIIa-His/His131 genotype is associated with enhanced susceptibility to PM infection in HIV-positive women but not in HIV-negative women. This study also provides the first evidence that the infant Fc?RIIa-His/His131 genotype is associated with susceptibility to perinatal HIV-1 transmission. There is no evidence for an association between HIV-positive child all-cause mortality and Fc?RIIa genotype.

References:

1. K.C. Brouwer , Renu B. Lal , Lisa B. Mirel , Chunfu Yang , Anne M. Van Eijk , John Ayisi , Juliana Otieno , Bernard L. Nahlen, Richard Steketee , Altaf A. Lal , Shi Y.P. Fc ( receptor IIa (CD32) polymorphism is associated with perinatal transmission of HIV-1 in western Kenya . AIDS 2004, 18: 1187-1194.
2. K.C. Brouwer, A.A. Lal, Lisa B. Mirel , Renu B. Lal, Anne M. Van Eijk , John Ayisi ,J.Otieno, R.Steketee, B.L. Nahlen, Shi Y.P. Association between genetic polymorphism in Fc receptor IIa for IgG (Fc ( RIIa) and placental malaria in western Kenya . JID 2004, 196: 1192-8