title: Can immune-related genotypes illuminate the immunopathogenesis of cytomegalovirus disease in human immunodeficiency virus-infected patients?
abstract: Most human immunodeficiency virus (HIV) patients are seropositive for cytomegalovirus (CMV) but a smaller proportion experience end-organ disease. This observation may reflect variations in genes affecting inflammatory and natural killer cell responses. DNA samples were collected from 240 HIV-infected patients followed at the University Hospitals/Case Medical Center (Cleveland, OH) between 1993 and 2008. Seventy-eight patients (African Americans = 41, Caucasians = 37) experienced CMV disease. Genotypes were determined using allele-specific fluorescent probes or multiplex polymerase chain reaction sequence-specific primers. IL12B3'UTR*(1) and SLC11A1 D543N*(1,2) were associated with CMV disease in African American patients (p = 0.04 and p = 0.02, respectively). IL10-1082*(1,2) and LILRB1 I142T*(1) were associated with CMV disease in Caucasians (p = 0.02 and p = 0.07, respectively). DARC T-46C*(1) and CD14 C-159T*(2) were associated with low nadir CD4(+) T cell counts in African American patients (p = 0.002 and p = 0.01, respectively). Caucasian patients carrying TNFA-308*2, TNFA-1031*(2), IL2-330*(1), CCL2-2518*(2), or LILRB1 I142T*(1) had significantly lower nadir CD4(+) T cells in a bootstrapped multivariable model (p = 0.006-0.02). In general, polymorphisms associated with CMV disease and CD4(+) T cell counts were distinct in Caucasian and African American patients in the United States. The LILRB1 I142T polymorphism was associated with both CMV disease and low nadir CD4(+) T cell counts in Caucasians, but the clearest determinant of low nadir CD4(+) T cell count in African American patients was DARC T-46C.
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Western Australia 6009, Australia.
authors.forename: Jacquita S
authors.initials: JS
authors.lastname: Affandi
authors.forename: Zayd K A
authors.initials: ZK
authors.lastname: Aghafar
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Sally
authors.initials: S
authors.lastname: Burrows
authors.forename: David
authors.initials: D
authors.lastname: Senitzer
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics