Browsing by Author "Castiblanco, John."

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Duffy-Null–Associated Low Neutrophil Counts Influence HIV-1 Susceptibility in High-Risk South African Black Women.
(Oxford University Press., 2010) Ramsuran, Veron.; Kulkarni, Hemant.; He, Weijing.; Mlisana, Koleka Patience.; Wright, Edwina J.; Werner, Lise.; Castiblanco, John.; Dhanda, Rahul.; Le, Tuan.; Dolan, Matthew J.; Guan, Weihua.; Weiss, Robin A.; Clark, Robert A.; Abdool Karim, Salim Safurdeen.; Ahuja, Sunil K.; Ndung'u, Peter Thumbi.
Background. The Duffy-null trait and ethnic netropenia are both highly prevalent in Africa. The influence of pre-seroconversion levels of peripheral blood cell counts (PBCs) on the risk of acquiring human immunodeficiency virus (HIV)–1 infection among Africans is unknown. Methods. The triangular relationship among pre-seroconversion PBC counts, host genotypes, and risk of HIV acquisition was determined in a prospective cohort of black South African high-risk female sex workers. Twenty seven women had seroconversion during follow-up, and 115 remained HIV negative for 2 years, despite engaging in high-risk activity. Results. Pre-seroconversion neutrophil counts in women who subsequently had seroconversion were significantly lower, whereas platelet counts were higher, compared with those who remained HIV negative. Comprising 27% of the cohort, subjects with pre-seroconversion neutrophil counts of <2500 cells/mm3 had a ~3-fold greater risk of acquiring HIV infection. In a genome-wide association analyses, an African-specific polymorphism (rs2814778) in the promoter of Duffy Antigen Receptor for Chemokines (DARC -46T>C) was significantly associated with neutrophil counts (P = 7.9 x10-11). DARC -46C/C results in loss of DARC expression on erthyrocytes (Duffy-null) and resistance to Plasmodium vivax malaria, and in our cohort, only subjects with this genotype had pre-seroconversion neutrophil counts of <2500 cells/mm3. The risk of acquiring HIV infection was ~3-fold greater in those with the trait of Duffy-null–associated low neutrophil counts, compared with all other study participants. Conclusions. Pre-seroconversion neutrophil and platelet counts influence risk of HIV infection. The trait of Duffy-null–associated low neutrophil counts influences HIV susceptibility. Because of the high prevalence of this trait among persons of African ancestry, it may contribute to the dynamics of the HIV epidemic in Africa.
Influence of variations in CCL3L1 and CCR5 on tuberculosis in a northwestern Colombian population.
(Oxford University Press on behalf of The Infectious Diseases Society of America., 2010) Mamtani, Manju.; Mummidi, Srinivas.; Ramsuran, Veron.; Pham, Minh-Hieu.; Maldonado, Robert.; Begum, Kazi.; Valera, Maria Soledad.; Sanchez, Racquel.; Castiblanco, John.; Kulkarni, Hemant.; Ndung'u, Peter Thumbi.; He, Weijing.; Anaya, Juan Manuel.; Ahuja, Sunil K.
We investigated the association of polymorphisms in CCR5, the major human immunodeficiency virus (HIV)–1 coreceptor, and copy number of its potent ligand CCL3L1 with tuberculosis in 298 individuals from Colombia. The CCR5-HHD haplotype, a known genetic determinant of increased susceptibility to HIV-AIDS, and a high copy number of CCL3L1, a known genetic determinant of enhanced CCL3/CCL3L1 chemokine expression, each associated with presence of tuberculosis. Furthermore, CCR5-HHD was associated with higher CCR5 gene and surface expression. These results substantiate the strong link between the pro-inflammatory effects of CCR5 and its ligands with active tuberculosis and suggest that chemokine-chemokine receptor genetic determinants may influence tuberculosis in addition to HIV/AIDS.