title: HLA class I, KIR, and genome-wide SNP diversity in the RV144 Thai phase 3 HIV vaccine clinical trial.
abstract: RV144 is the first phase 3 HIV vaccine clinical trial to demonstrate efficacy. This study consisted of more than 8,000 individuals in each arm of the trial, representing the four major regions of Thailand. Human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptor (KIR) genes, as well as 96 genome-wide ancestry informative markers (AIMs) were genotyped in 450 placebo HIV-1-uninfected individuals to identify the immunogenetic diversity and population structure of this cohort. High-resolution genotyping identified the common HLA alleles as A*02:03, A*02:07, A*11:01, A*24:02, A*24:07, A*33:03, B*13:01, B*15:02, B*18:01, B*40:01, B*44:03, B*46:01, B*58:01, C*01:02, C*03:02, C*03:04, C*07:01, C*07:02, C*07:04, and C*08:01. The most frequent three-loci haplotype was B*46:01-C*01:02-A*02:07. Framework genes KIR2DL4, 3DL2, and 3DL3 were present in all samples, and KIR2DL1, 2DL3, 3DL1, 2DS4, and 2DP1 occurred at frequencies greater than 90 %. The combined HLA and KIR profile suggests admixture with neighboring Asian populations. Principal component and correspondence analyses comparing the RV144 samples to the phase 3 International HapMap Project (HapMap3) populations using AIMs corroborated these findings. Structure analyses identified a distinct profile in the Thai population that did not match the Asian or other HapMap3 samples. This shows genetic variability unique to Thais in RV144, making it essential to take into account population stratification while performing genetic association studies. The overall analyses from all three genetic markers indicate that the RV144 samples are representative of the Thai population. This will inform subsequent host genetic analyses in the RV144 cohort and provide insight for future genetic association studies in the Thai population.
authors.affiliation: U.S. Military HIV Research Program (MHRP), Walter Reed Army Institute of Research, Silver Spring, MD, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Prentice
authors.forename: Philip K
authors.initials: PK
authors.lastname: Ehrenberg
authors.forename: Karen M
authors.initials: KM
authors.lastname: Baldwin
authors.forename: Aviva
authors.initials: A
authors.lastname: Geretz
authors.forename: Charla
authors.initials: C
authors.lastname: Andrews
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Connell
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Rasmi
authors.initials: R
authors.lastname: Thomas
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000483:Alleles; D004843:Epistasis, Genetic; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D054340:Receptors, KIR / Q000235:genetics*
chemical_list: D016915:AIDS Vaccines; D005819:Genetic Markers; D015395:Histocompatibility Antigens Class I; D054340:Receptors, KIR